2-(1h-indazol-3-yl)-3h-imidazo[4,5-b]pyridine and therapeutic uses thereof

ABSTRACT

Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

RELATED APPLICATIONS

This application is a continuation application of U.S. application Ser.No. 14/847,336, filed Sep. 8, 2015, and claims the benefit of U.S.Provisional Application No. 62/047,401, filed Sep. 8, 2014, which isincorporated herein by reference in its entirety.

BACKGROUND Technical Field

This disclosure relates to inhibitors of one or more proteins in the Wntpathway, including inhibitors of one or more Wnt proteins, andcompositions comprising the same. More particularly, it concerns the useof an indazole compound or salts or analogs thereof, in the treatment ofdisorders characterized by the activation of Wnt pathway signaling(e.g., cancer, abnormal cellular proliferation, angiogenesis, fibroticdisorders, bone or cartilage diseases, and osteoarthritis), themodulation of cellular events mediated by Wnt pathway signaling, as wellas genetic diseases and neurological conditions/disorders/diseases dueto mutations or dysregulation of the Wnt pathway and/or of one or moreof Wnt signaling components. Also provided are methods for treatingWnt-related disease states.

Background

The Wnt growth factor family includes more than 10 genes identified inthe mouse and at least 19 genes identified in the human. Members of theWnt family of signaling molecules mediate many short-and long-rangepatterning processes during invertebrate and vertebrate development. TheWnt signaling pathway is known for its role in the inductiveinteractions that regulate growth and differentiation, and it also playsroles in the homeostatic maintenance of post-embryonic tissue integrity.Wnt stabilizes cytoplasmic β-catenin, which stimulates the expression ofgenes including c-myc, c jun, fra-1, and cyclin Dl. In addition,misregulation of Wnt signaling can cause developmental defects and isimplicated in the genesis of several human cancers. The Wnt pathway hasalso been implicated in the maintenance of stem or progenitor cells in agrowing list of adult tissues including skin, blood, gut, prostate,muscle, and the nervous system.

SUMMARY

The present disclosure provides methods and reagents, involvingcontacting a cell with an agent, such as an indazole compound, in asufficient amount to antagonize a Wnt activity, e.g., to reverse orcontrol an aberrant growth state or correct a genetic disorder due tomutations in Wnt signaling components.

Some embodiments disclosed herein include Wnt inhibitors containing anindazole core. Other embodiments disclosed herein include pharmaceuticalcompositions and methods of treatment using these compounds.

One embodiment disclosed herein includes a compound having the structureof Formula I:

as well as prodrugs and pharmaceutically acceptable salts thereof.

In some embodiments of Formula (I):

R¹, R², and R⁴ are independently selected from the group consisting of Hand halide;

R³ is selected from the group consisting of -heteroaryl(R⁶)_(q) and-heterocyclyl(R⁷)_(h);

R⁵ is selected from the group consisting of H, -heteroaryl(R⁸)_(q),-heterocyclyl(R⁹)_(h), and -aryl(R¹⁰)_(k);

-   -   each R⁶ is one substituent attached to the heteroaryl and is        independently selected from the group consisting of halide,        —(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R¹¹)_(h), —(C₁₋₄        alkylene)_(p)carbocyclyl(R¹²)_(j), —(C₁₋₄        alkylene)_(p)aryl(R¹³)_(k), —NHC(═O)R¹⁴, —NR¹⁵R¹⁶, —(C₁₋₆        alkylene)NR¹⁷R¹⁸, and —OR²⁴;    -   each R⁷ is one substituent attached to the heterocyclyl and is        independently selected from the group consisting of —(C₁₋₄        alkyl), halide, —CF₃, and —CN;    -   each R⁸ is one substituent attached to the heteroaryl and is        independently selected from the group consisting of —(C₁₋₆        alkyl), halide, —CF₃, —OCH₃, —CN, and —C(═O)R¹⁹;    -   each R⁹ is one substituent attached to the heterocyclyl and is        independently selected from the group consisting of —(C₁₋₆        alkyl), halide, —CF₃, —CN, and —OCH₃;    -   each R¹⁰ is one substituent attached to the aryl and is        independently selected from the group consisting of —(C₁₋₆        alkyl), halide, —CF₃, —CN, —OCH₃, —(C₁₋₆ alkylene)_(p)NHSO₂R¹⁹,        —NR¹⁵(C₁₋₆alkylene)NR¹⁵R¹⁶, —(C₁₋₆ alkylene)_(p)NR¹⁵R¹⁶, and        —OR²⁷;    -   each R¹¹ is one substituent attached to the heterocyclyl and is        independently selected from the group consisting of amino,        —(C₁₋₄ alkyl), halide, —CF₃, and —CN;    -   each R¹² is one substituent attached to the carbocyclyl and is        independently selected from the group consisting of —(C₁₋₄        alkyl), halide, —CF₃, and —CN;    -   each R¹³ is one substituent attached to the aryl and is        independently selected from the group consisting of —(C₁₋₄        alkyl), halide, —CF₃, and —CN;    -   each R¹⁴ is independently selected from the group consisting of        —(C₁₋₉ alkyl), -heteroaryl(R²⁰)_(q), -aryl(R²¹)_(k),        —CH₂aryl(R²¹)_(k), -carbocyclyl(R²²), —CH₂carbocyclyl(R²²)_(j),        —(C₁₋₄ alkylene)_(p)NR²⁵R²⁶, -heterocyclyl(R²³)_(h), and        —CH₂heterocyclyl(R²³)_(h);    -   each R¹⁵ is independently selected from the group consisting of        H and —(C₁₋₆ alkyl);    -   each R¹⁶ is independently selected from the group consisting of        H, —(C₁₋₆ alkyl), —CH₂aryl(R²¹)_(k), and        —CH₂carbocyclyl(R²²)_(j);    -   each R¹⁷ is independently selected from the group consisting of        H and —(C₁₋₆ alkyl);    -   each R¹⁸ is independently selected from the group consisting of        H, —(C₁₋₆ alkyl), —CH₂aryl(R²¹)_(k), and        —CH₂carbocyclyl(R²²)_(j);    -   each R¹⁹ is a —(C₁₋₆ alkyl);    -   each R²⁰ is one substituent attached to the heteroaryl and is        independently selected from the group consisting of —(C₁₋₄        alkyl), halide, —CF₃, and —CN;    -   each R²¹ is one substituent attached to the aryl and is        independently selected from the group consisting of —(C₁₋₄        alkyl), halide, —CF₃, and —CN;    -   each R²² is one substituent attached to the carbocyclyl and is        independently selected from the group consisting of —(C₁₋₄        alkyl), halide, —CF₃, and —CN;    -   each R²³ is one substituent attached to the heterocyclyl and is        independently selected from the group consisting of —(C₁₋₄        alkyl), halide, —CF₃, and —CN;    -   each R²⁴ is independently selected from the group consisting of        H, —(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R²³)_(h),        —(C₁₋₄ alkylene)_(p)carbocyclyl(R²²)_(j), —(C₁₋₄        alkylene)_(p)aryl(R²¹)_(k), and —(C₁₋₆ alkylene)_(p)NR²⁵R²⁶;    -   each R²⁵ is independently selected from the group consisting of        H and —(C₁₋₆ alkyl);    -   each R²⁶ is independently selected from the group consisting of        H and —(C₁₋₆ alkyl);    -   each R²⁷ is independently selected from the group consisting of        H, —(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R²³)_(h), and        —(C₁₋₆ alkylene)_(p)NR²⁵R²⁶;    -   each p is independently 0 or 1;    -   each q is independently 0 to 4;    -   each h is independently 0 to 10;    -   each k is independently 0 to 5; and    -   each j is independently 0 to 12.

Some embodiments include stereoisomers and pharmaceutically acceptablesalts of a compound of Formula (I).

Some embodiments include pro-drugs of a compound of Formula (I).

Some embodiments of the present disclosure include pharmaceuticalcompositions comprising a compound of Formula (I) and a pharmaceuticallyacceptable carrier, diluent, or excipient.

Other embodiments disclosed herein include methods of inhibiting one ormore members of the Wnt pathway, including one or more Wnt proteins byadministering to a patient affected by a disorder or disease in whichaberrant Wnt signaling is implicated, such as cancer and other diseasesassociated with abnormal angiogenesis, cellular proliferation, cellcycling and mutations in Wnt signaling components, a compound accordingto Formula (I). Accordingly, the compounds and compositions providedherein can be used to treat cancer, to reduce or inhibit angiogenesis,to reduce or inhibit cellular proliferation and correct a geneticdisorder due to mutations in Wnt signaling components.

Non-limiting examples of diseases which can be treated with thecompounds and compositions provided herein include a variety of cancers,diabetic retinopathy, pulmonary fibrosis, rheumatoid arthritis, sepsis,anklyosing spondylitis, psoriasis, scleroderma, mycotic and viralinfections, osteochondrodysplasia, Alzheimer's disease, lung disease,bone/osteoporotic (wrist, spine, shoulder and hip) fractures, articularcartilage (chondral) defects, degenerative disc disease (orintervertebral disc degeneration), polyposis coli,osteoporosis-pseudoglioma syndrome, familial exudativevitreoretinopathy, retinal angiogenesis, early coronary disease,tetra-Amelia syndrome, Müllerian-duct regression and virilization,SERKAL syndrome, diabetes mellitus type 2, Fuhrmann syndrome,Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome,odonto-onycho-dermal dysplasia, obesity, split-hand/foot malformation,caudal duplication syndrome, tooth agenesis, Wilms tumor, skeletaldysplasia, focal dermal hypoplasia, autosomal recessive anonychia,neural tube defects, alpha-thalassemia (ATRX) syndrome, fragile Xsyndrome, ICF syndrome, Angelman syndrome, Prader-Willi syndrome,Beckwith-Wiedemann Syndrome, Norrie disease, and Rett syndrome.

Some embodiments of the present disclosure include methods to preparecompounds of Formula (I).

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are not restrictive of the invention, as claimed.

DETAILED DESCRIPTION

Provided herein are compositions and methods for inhibiting one or moremembers of the Wnt pathway, including one or more Wnt proteins. OtherWnt inhibitors and methods for using the same are disclosed in U.S.application Ser. Nos. 12/852,706; 12/968,505; 13/552,188; 13/800,963;13/855,874; 13/887,177 13/938,691; 13/938,692; 14/019,103; 14/019,147;14/019,940; 14/149,948; 14/178,749; 14/331,427; and Ser. No. 14/334,005;and U.S. Provisional Application Ser. Nos. 61/232,603; 61/288,544;61/305,459; 61/620,107; 61/642,915; and 61/750,221, all of which areincorporated by reference in their entirety herein.

Some embodiments provided herein relate to a method for treating adisease or disorder including, but not limited to, cancers, diabeticretinopathy, pulmonary fibrosis, rheumatoid arthritis, sepsis,anklyosing spondylitis, psoriasis, scleroderma, mycotic and viralinfections, bone and cartilage diseases, Alzheimer's disease, lungdisease, osteoarthritis, bone/osteoporotic (wrist, spine, shoulder andhip) fractures, articular cartilage (chondral) defects, degenerativedisc disease (or intervertebral disc degeneration), polyposis coli, bonedensity and vascular defects in the eye (Osteoporosis-pseudogliomaSyndrome, OPPG) and other eye diseases or syndromes associated withdefects or damaged photoreceptors, familial exudative vitreoretinopathy,retinal angiogenesis, early coronary disease, tetra-amelia,Müllerian-duct regression and virilization, SERKAL syndrome, type IIdiabetes, Fuhrmann syndrome, Al-Awadi/Raas-Rothschild/Schinzelphocomelia syndrome, odonto-onycho-dermal dysplasia, obesity,split-hand/foot malformation, caudal duplication, tooth agenesis, Wilmstumor, skeletal dysplasia, focal dermal hypoplasia, autosomal recessiveanonychia, neural tube defects, alpha-thalassemia (ATRX) syndrome,fragile X syndrome, ICF syndrome, Angelman's syndrome, Prader-Willisyndrome, Beckwith-Wiedemann Syndrome, Norrie disease, and Rettsyndrome.

In some embodiments, non-limiting examples of bone and cartilagediseases which can be treated with the compounds and compositionsprovided herein include bone spur (osteophytes), craniosynostosis,fibrodysplasia ossificans progressive, fibrous dysplasia, giant celltumor of bone, hip labral tear, meniscal tears, bone/osteoporotic(wrist, spine, shoulder and hip) fractures, articular cartilage(chondral) defects, degenerative disc disease (or intervertebral discdegeneration), osteochondritis dissecans, osteochondroma (bone tumor),osteopetrosis, relapsing polychondritis, and Salter-Harris fractures.

In some embodiments, pharmaceutical compositions are provided that areeffective for treatment of a disease of an animal, e.g., a mammal,caused by the pathological activation or mutations of the Wnt pathway.The composition includes a pharmaceutically acceptable carrier and acompound as described herein.

Definitions

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as is commonly understood by one of ordinary skillin the art to which this disclosure belongs. All patents, applications,published applications, and other publications are incorporated byreference in their entirety. In the event that there is a plurality ofdefinitions for a term herein, those in this section prevail unlessstated otherwise.

As used herein, “alkyl” means a branched, or straight chain chemicalgroup containing only carbon and hydrogen, such as methyl, ethyl,n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, sec-pentyl and neo-pentyl. Alkyl groups can eitherbe unsubstituted or substituted with one or more substituents. Alkylgroups can be saturated or unsaturated (e.g., containing —C═C— or —C≡C—subunits), at one or several positions. In some embodiments, alkylgroups include 1 to 9 carbon atoms (for example, 1 to 6 carbon atoms, 1to 4 carbon atoms, or 1 to 2 carbon atoms).

As used herein, “alkylene” means a bivalent branched, or straight chainchemical group containing only carbon and hydrogen, such as methylene,ethylene, n-propylene, iso-propylene, n-butylene, iso-butylene,sec-butylene, tert-butylene, n-pentylene, iso-pentylene, sec-pentyleneand neo-pentylene. Alkylene groups can either be unsubstituted orsubstituted with one or more substituents. Alkylene groups can besaturated or unsaturated (e.g., containing —C═C— or —C≡C— subunits), atone or several positions. In some embodiments, alkylene groups include 1to 9 carbon atoms (for example, 1 to 6 carbon atoms, 1 to 4 carbonatoms, or 1 to 2 carbon atoms).

As used herein, “carbocyclyl” means a cyclic ring system containing onlycarbon atoms in the ring system backbone, such as cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, and cyclohexenyl. Carbocyclyls mayinclude multiple fused rings. Carbocyclyls may have any degree ofsaturation provided that at least one ring in the ring system is notaromatic. Carbocyclyl groups can either be unsubstituted or substitutedwith one or more substituents. In some embodiments, carbocyclyl groupsinclude 3 to 10 carbon atoms, for example, 3 to 6 carbon atoms.

As used herein, “lower alkyl” means a subset of alkyl having 1 to 3carbon atoms, which is linear or branched. Examples of lower alkylsinclude methyl, ethyl, n-propyl and isopropyl. Likewise, radicals usingthe terminology “lower” refer to radicals having 1 to about 3 carbons inthe alkyl portion of the radical.

As used herein, “aryl” means a mono-, bi-, tri- or polycyclic group withonly carbon atoms present in the ring backbone having 5 to 14 ringatoms, alternatively 5, 6, 9, or 10 ring atoms; and having 6, 10, or 14pi electrons shared in a cyclic array; wherein at least one ring in thesystem is aromatic. Aryl groups can either be unsubstituted orsubstituted with one or more substituents. Examples of aryl includephenyl, naphthyl, tetrahydronaphthyl, 2,3-dihydro-1H-indenyl, andothers. In some embodiments, the aryl is phenyl.

As used herein, “arylalkyl” means an aryl-alkyl- group in which the aryland alkyl moieties are as previously described. In some embodiments,arylalkyl groups contain a C₁₋₄alkyl moiety. Exemplary arylalkyl groupsinclude benzyl and 2-phenethyl.

As used herein, the term “heteroaryl” means a mono-, bi-, tri- orpolycyclic group having 5 to 14 ring atoms, alternatively 5, 6, 9, or 10ring atoms; and having 6, 10, or 14 pi electrons shared in a cyclicarray; wherein at least one ring in the system is aromatic, and at leastone ring in the system contains one or more heteroatoms independentlyselected from the group consisting of N, O, and S. Heteroaryl groups caneither be unsubstituted or substituted with one or more substituents.Examples of heteroaryl include thienyl, pyridinyl, furyl, oxazolyl,oxadiazolyl, pyrrolyl, imidazolyl, triazolyl, thiodiazolyl, pyrazolyl,isoxazolyl, thiadiazolyl, pyranyl, pyrazinyl, pyrimidinyl, pyridazinyl,triazinyl, thiazolyl benzothienyl, benzoxadiazolyl, benzofuranyl,benzimidazolyl, benzotriazolyl, cinnolinyl, indazolyl, indolyl,isoquinolinyl, isothiazolyl, naphthyridinyl, purinyl, thienopyridinyl,pyrido[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyridinyl, quinazolinyl,quinolinyl, thieno[2,3-c]pyridinyl, pyrazolo[3,4-b]pyridinyl,pyrazolo[3,4-c]pyridinyl, pyrazolo[4,3-c]pyridine,pyrazolo[4,3-b]pyridinyl, tetrazolyl, chromane,2,3-dihydrobenzo[b][1,4]dioxine, benzo[d][1,3]dioxole,2,3-dihydrobenzofuran, 2,3-dihydrobenzo[b][1,4]oxathiine, and others. Insome embodiments, the heteroaryl is selected from thienyl, pyridinyl,furyl, pyrazolyl, imidazolyl, pyranyl, pyrazinyl, and pyrimidinyl.

As used herein, “halo”, “halide” or “halogen” is a chloro, bromo,fluoro, or iodo atom radical. In some embodiments, a halo is a chloro,bromo or fluoro. For example, a halide can be fluoro.

As used herein, “haloalkyl” means a hydrocarbon substituent, which is alinear or branched, alkyl, alkenyl or alkynyl substituted with one ormore chloro, bromo, fluoro, and/or iodo atom(s). In some embodiments, ahaloalkyl is a fluoroalkyls, wherein one or more of the hydrogen atomshave been substituted by fluoro. In some embodiments, haloalkyls are of1 to about 3 carbons in length (e.g., 1 to about 2 carbons in length or1 carbon in length). The term “haloalkylene” means a diradical variantof haloalkyl, and such diradicals may act as spacers between radicals,other atoms, or between a ring and another functional group.

As used herein, “heterocyclyl” means a nonaromatic cyclic ring systemcomprising at least one heteroatom in the ring system backbone.Heterocyclyls may include multiple fused rings. Heterocyclyls may besubstituted or unsubstituted with one or more substituents. In someembodiments, heterocycles have 5-7 members. In six membered monocyclicheterocycles, the heteroatom(s) are selected from one to three of O, Nor S, and wherein when the heterocycle is five membered, it can have oneor two heteroatoms selected from O, N, or S. Examples of heterocyclylinclude azirinyl, aziridinyl, azetidinyl, oxetanyl, thietanyl,1,4,2-dithiazolyl, dihydropyridinyl, 1,3-dioxanyl, 1,4-dioxanyl,1,3-dioxolanyl, morpholinyl, thiomorpholinyl, piperazinyl, pyranyl,pyrrolidinyl, tetrahydrofuryl, tetrahydropyridinyl, oxazinyl, thiazinyl,thiinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isoxazolidinyl,piperidinyl, pyrazolidinyl imidazolidinyl, thiomorpholinyl, and others.In some embodiments, the heterocyclyl is selected from azetidinyl,morpholinyl, piperazinyl, pyrrolidinyl, and tetrahydropyridinyl.

As used herein, “monocyclic heterocyclyl” means a single nonaromaticcyclic ring comprising at least one heteroatom in the ring systembackbone. Heterocyclyls may be substituted or unsubstituted with one ormore substituents. In some embodiments, heterocycles have 5-7 members.In six membered monocyclic heterocycles, the heteroatom(s) are selectedfrom one to three of O, N or S, and wherein when the heterocycle is fivemembered, it can have one or two heteroatoms selected from O, N, or S.Examples of heterocyclyl include azirinyl, aziridinyl, azetidinyl,oxetanyl, thietanyl, 1,4,2-dithiazolyl, dihydropyridinyl, 1,3-dioxanyl,1,4-dioxanyl, 1,3-dioxolanyl, morpholinyl, thiomorpholinyl, piperazinyl,pyranyl, pyrrolidinyl, tetrahydrofuryl, tetrahydropyridinyl, oxazinyl,thiazinyl, thiinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl,isoxazolidinyl, piperidinyl, pyrazolidinyl imidazolidinyl,thiomorpholinyl, and others.

The term “substituted” refers to moieties having substituents replacinga hydrogen on one or more non-hydrogen atoms of the molecule. It will beunderstood that “substitution” or “substituted with” includes theimplicit proviso that such substitution is in accordance with permittedvalence of the substituted atom and the substituent, and that thesubstitution results in a stable compound, e.g., which does notspontaneously undergo transformation such as by rearrangement,cyclization, elimination, etc. Substituents can include, for example,—(C₁₋₉ alkyl) optionally substituted with one or more of hydroxyl, —NH₂,—NH(C₁₋₃ alkyl), and —N(C₁₋₃ alkyl)₂; —(C₁₋₉ haloalkyl); a halide; ahydroxyl; a carbonyl [such as —C(O)OR, and —C(O)R]; a thiocarbonyl [suchas —C(S)OR, —C(O)SR, and —C(S)R]; —(C₁₋₉ alkoxyl) optionally substitutedwith one or more of halide, hydroxyl, —NH₂, —NH(C₁₋₃ alkyl), and —N(C₁₋₃alkyl)₂; —OPO(OH)₂; a phosphonate [such as —PO(OH)₂ and —PO(OR′)₂];—OPO(OR′)R″; —NRR′; —C(O)NRR′; —C(NR)NR′R″; —C(NR′)R″; a cyano; a nitro;an azido; —SH; —S—R; —OSO₂(OR); a sulfonate [such as —SO₂(OH) and—SO₂(OR)]; —SO₂NR′R″; and —SO₂R; in which each occurrence of R, R′ andR″ are independently selected from H; —(C₁₋₉ alkyl); C₆₋₁₀ aryloptionally substituted with from 1-3R′″; 5-10 membered heteroaryl havingfrom 1-4 heteroatoms independently selected from N, O, and S andoptionally substituted with from 1-3 R′″; C₃₋₇ carbocyclyl optionallysubstituted with from 1-3 R′″; and 3-8 membered heterocyclyl having from1-4 heteroatoms independently selected from N, O, and S and optionallysubstituted with from 1-3 R′″; wherein each R′″ is independentlyselected from —(C₁₋₆ alkyl), —(C₁₋₆ haloalkyl), a halide (e.g., F), ahydroxyl, —C(O)OR, —C(O)R, —(C₁₋₆ alkoxyl), —NRR′, —C(O)NRR′, and acyano, in which each occurrence of R and R′ is independently selectedfrom H and —(C₁₋₆ alkyl). In some embodiments, the substituent isselected from —(C₁₋₆ alkyl), —(C₁₋₆ haloalkyl), a halide (e.g., F), ahydroxyl, —C(O)OR, —C(O)R, —(C₁₋₆ alkoxyl), —NRR′, —C(O)NRR′, and acyano, in which each occurrence of R and R′ is independently selectedfrom H and —(C₁₋₆ alkyl).

As used herein, when two groups are indicated to be “linked” or “bonded”to form a “ring”, it is to be understood that a bond is formed betweenthe two groups and may involve replacement of a hydrogen atom on one orboth groups with the bond, thereby forming a carbocyclyl, heterocyclyl,aryl, or heteroaryl ring. The skilled artisan will recognize that suchrings can and are readily formed by routine chemical reactions. In someembodiments, such rings have from 3-7 members, for example, 5 or 6members.

The skilled artisan will recognize that some structures described hereinmay be resonance forms or tautomers of compounds that may be fairlyrepresented by other chemical structures, even when kinetically, theartisan recognizes that such structures are only a very small portion ofa sample of such compound(s). Such compounds are clearly contemplatedwithin the scope of this disclosure, though such resonance forms ortautomers are not represented herein.

The compounds provided herein may encompass various stereochemicalforms. The compounds also encompass diastereomers as well as opticalisomers, e.g., mixtures of enantiomers including racemic mixtures, aswell as individual enantiomers and diastereomers, which arise as aconsequence of structural asymmetry in certain compounds. Separation ofthe individual isomers or selective synthesis of the individual isomersis accomplished by application of various methods which are well knownto practitioners in the art. Unless otherwise indicated, when adisclosed compound is named or depicted by a structure withoutspecifying the stereochemistry and has one or more chiral centers, it isunderstood to represent all possible stereoisomers of the compound.

The term “administration” or “administering” refers to a method ofproviding a dosage of a compound or pharmaceutical composition to avertebrate or invertebrate, including a mammal, a bird, a fish, or anamphibian, where the method is, e.g., orally, subcutaneously,intravenously, intralymphatic, intranasally, topically, transdermally,intraperitoneally, intramuscularly, intrapulmonarilly, vaginally,rectally, ontologically, neuro-otologically, intraocularly,subconjuctivally, via anterior eye chamber injection, intravitreally,intraperitoneally, intrathecally, intracystically, intrapleurally, viawound irrigation, intrabuccally, intra-abdominally, intra-articularly,intra-aurally, intrabronchially, intracapsularly, intrameningeally, viainhalation, via endotracheal or endobronchial instillation, via directinstillation into pulmonary cavities, intraspinally, intrasynovially,intrathoracically, via thoracostomy irrigation, epidurally,intratympanically, intracisternally, intravascularly,intraventricularly, intraosseously, via irrigation of infected bone, orvia application as part of any admixture with a prosthetic device. Themethod of administration can vary depending on various factors, e.g.,the components of the pharmaceutical composition, the site of thedisease, the disease involved, and the severity of the disease.

A “diagnostic” as used herein is a compound, method, system, or devicethat assists in the identification or characterization of a health ordisease state. The diagnostic can be used in standard assays as is knownin the art.

The term “mammal” is used in its usual biological sense. Thus, itspecifically includes humans, cattle, horses, monkeys, dogs, cats, mice,rats, cows, sheep, pigs, goats, and non-human primates, but alsoincludes many other species.

The term “pharmaceutically acceptable carrier”, “pharmaceuticallyacceptable diluent” or “pharmaceutically acceptable excipient” includesany and all solvents, co-solvents, complexing agents, dispersion media,coatings, isotonic and absorption delaying agents and the like which arenot biologically or otherwise undesirable. The use of such media andagents for pharmaceutically active substances is well known in the art.Except insofar as any conventional media or agent is incompatible withthe active ingredient, its use in the therapeutic compositions iscontemplated. Supplementary active ingredients can also be incorporatedinto the compositions. In addition, various adjuvants such as arecommonly used in the art may be included. These and other such compoundsare described in the literature, e.g., in the Merck Index, Merck &Company, Rahway, N.J. Considerations for the inclusion of variouscomponents in pharmaceutical compositions are described, e.g., in Gilmanet al. (Eds.) (2010); Goodman and Gilman's: The Pharmacological Basis ofTherapeutics, 12th Ed., The McGraw-Hill Companies.

The term “pharmaceutically acceptable salt” refers to salts that retainthe biological effectiveness and properties of the compounds providedherein and, which are not biologically or otherwise undesirable. In manycases, the compounds provided herein are capable of forming acid and/orbase salts by virtue of the presence of amino and/or carboxyl groups orgroups similar thereto. Many such salts are known in the art, forexample, as described in WO 87/05297. Pharmaceutically acceptable acidaddition salts can be formed with inorganic acids and organic acids.Inorganic acids from which salts can be derived include, for example,hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid,phosphoric acid, and the like. Organic acids from which salts can bederived include, for example, acetic acid, propionic acid, glycolicacid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinicacid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamicacid, mandelic acid, methanesulfonic acid, ethanesulfonic acid,p-toluenesulfonic acid, salicylic acid, and the like. Pharmaceuticallyacceptable base addition salts can be formed with inorganic and organicbases. Inorganic bases from which salts can be derived include, forexample, sodium, potassium, lithium, ammonium, calcium, magnesium, iron,zinc, copper, manganese, aluminum, and the like; particularly preferredare the ammonium, potassium, sodium, calcium, and magnesium salts.Organic bases from which salts can be derived include, for example,primary, secondary, and tertiary amines, substituted amines includingnaturally occurring substituted amines, cyclic amines, basic ionexchange resins, and the like, specifically such as isopropylamine,trimethylamine, diethylamine, triethylamine, tripropylamine, andethanolamine.

“Solvate” refers to the compound formed by the interaction of a solventand a compound as provided herein or a salt thereof. Suitable solvatesare pharmaceutically acceptable solvates including hydrates.

“Patient” as used herein, means a human or a non-human mammal, e.g., adog, a cat, a mouse, a rat, a cow, a sheep, a pig, a goat, a non-humanprimate, or a bird, e.g., a chicken, as well as any other vertebrate orinvertebrate. In some embodiments, the patient is a human.

A “therapeutically effective amount” or “pharmaceutically effectiveamount” of a compound as provided herein is one which is sufficient toachieve the desired physiological effect and may vary according to thenature and severity of the disease condition, and the potency of thecompound. “Therapeutically effective amount” is also intended to includeone or more of the compounds of Formula I in combination with one ormore other agents that are effective to treat the diseases and/orconditions described herein. The combination of compounds can be asynergistic combination. Synergy, as described, for example, by Chou andTalalay, Advances in Enzyme Regulation (1984), 22, 27-55, occurs whenthe effect of the compounds when administered in combination is greaterthan the additive effect of the compounds when administered alone as asingle agent. In general, a synergistic effect is most clearlydemonstrated at sub-optimal concentrations of the compounds. It will beappreciated that different concentrations may be employed forprophylaxis than for treatment of an active disease. This amount canfurther depend upon the patient's height, weight, sex, age and medicalhistory.

A therapeutic effect relieves, to some extent, one or more of thesymptoms of the disease.

“Treat,” “treatment,” or “treating,” as used herein refers toadministering a compound or pharmaceutical composition as providedherein for therapeutic purposes. The term “therapeutic treatment” refersto administering treatment to a patient already suffering from a diseasethus causing a therapeutically beneficial effect, such as amelioratingexisting symptoms, ameliorating the underlying metabolic causes ofsymptoms, postponing or preventing the further development of adisorder, and/or reducing the severity of symptoms that will or areexpected to develop.

“Drug-eluting” and/or controlled release as used herein refers to anyand all mechanisms, e.g., diffusion, migration, permeation, and/ordesorption by which the drug(s) incorporated in the drug-elutingmaterial pass therefrom over time into the surrounding body tissue.

“Drug-eluting material” and/or controlled release material as usedherein refers to any natural, synthetic or semi-synthetic materialcapable of acquiring and retaining a desired shape or configuration andinto which one or more drugs can be incorporated and from whichincorporated drug(s) are capable of eluting over time.

“Elutable drug” as used herein refers to any drug or combination ofdrugs having the ability to pass over time from the drug-elutingmaterial in which it is incorporated into the surrounding areas of thebody.

The term “comprising” as used herein is synonymous with “including,”“containing,” or “characterized by,” and is inclusive or open-ended anddoes not exclude additional, unrecited elements or method steps.

Compounds

The compounds and compositions described herein can be used asanti-proliferative agents, e.g., anti-cancer and anti-angiogenesisagents, and/or as inhibitors of the Wnt signaling pathway, e.g., fortreating diseases or disorders associated with aberrant Wnt signaling.In addition, the compounds can be used as inhibitors of one or morekinases, kinase receptors, or kinase complexes. Such compounds andcompositions are also useful for controlling cellular proliferation,differentiation, and/or apoptosis.

Some embodiments of the present disclosure include compounds of FormulaI:

or salts, pharmaceutically acceptable salts, or prodrugs thereof.

In some embodiments, R¹, R², and R⁴ are independently selected from thegroup consisting of H and halide.

In some embodiments, R³ is selected from the group consisting of-pyridinyl(R⁶)_(q) and -pyrimidinyl(R⁷)_(q).

In some embodiments, R³ is selected from the group consisting of-piperidinyl(R⁷)_(h) and -tetrahydropyridinyl(R⁷)_(h).

In some embodiments, R³ is selected from the group consisting of-pyridinyl(R⁶)_(q), -pyrimidinyl(R⁶)_(q), -pyrazinyl(R⁶)_(q),-pyrazolyl(R⁶)_(q), and -imidazolyl(R⁶)_(q).

In some embodiments, R³ is selected from the group consisting of-heteroaryl(R⁶)_(q) and -heterocyclyl(R⁷)_(h).

In some embodiments, R⁵ is selected from the group consisting of H,-heteroaryl(R⁸)_(q), -heterocyclyl(R⁹)_(h), and -aryl(R¹⁰)_(k).

In some embodiments, R⁵ is selected from the group consisting of H,-pyridinyl(R⁸)_(q), -imidazolyl(R⁸)_(q), -furanyl(R⁸)_(q),-thiophenyl(R⁸)_(q), -piperidinyl(R⁹)_(h), -piperazinyl(R⁹)_(h), and-phenyl(R¹⁰)_(k).

In some embodiments, each R⁶ is one substituent attached to thepyridinyl and is independently selected from the group consisting of H,halide, —(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R¹¹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹²)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹³)_(k),—NHC(═O)R⁴, —NR¹⁵R¹⁶, —(C₁₋₆ alkylene)NR¹⁷R¹⁸, and —OR²⁴.

In some embodiments, each R⁶ is one substituent attached to thepyridinyl and is independently selected from the group consisting ofhalide, —(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R¹¹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹²)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹³)_(k),—NHC(═O)R⁴, —NR¹⁵R¹⁶, —(C₁₋₆ alkylene)NR¹⁷R¹⁸, and —OR²⁴.

In some embodiments, each R⁶ is one substituent attached to theheteroaryl and is independently selected from the group consisting of H,halide, —(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R¹¹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹²)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹³)_(k),—NHC(═O)R⁴, —NR¹⁵R¹⁶, —(C₁₋₆ alkylene)NR¹⁷R¹⁸, and —OR²⁴.

In some embodiments, each R⁶ is one substituent attached to theheteroaryl and is independently selected from the group consisting ofhalide, —(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R⁸)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹²)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹³)_(k),—NHC(═O)R⁴, —NR¹⁵R¹⁶, —(C₁₋₆ alkylene)NR¹⁷R¹⁸, and —OR²⁴.

In some embodiments, each R⁶ is one substituent attached to theheteroaryl and is independently selected from the group consisting of F,-Me, -Et, —(CH₂)heterocyclyl(R¹¹)_(h), -heterocyclyl(R¹¹)_(h),—(CH₂)carbocyclyl(R²)_(j), —(CH₂)aryl(R³)_(k), —NHC(═O)(C₁₋₅ alkyl),—NHC(═O)phenyl(R²¹)_(k), —NHC(═O)(CH₂)phenyl(R²¹)_(k),—NHC(═O)carbocyclyl(R²²)_(j), —NHC(═O)(CH₂)heterocyclyl(R²³)_(h), —NH₂,—N(C₁₋₃ alkyl)₂, —NH(C₁₋₄ alkyl), —(CH₂)N(C₁₋₃ alkyl)₂, —(CH₂)NH(C₁₋₄alkyl), —OH, —O(C₁₋₃ alkyl), —Ocarbocyclyl(R²²)_(j),—Oheterocyclyl(R²³)_(h), —O(CH₂CH₂)heterocyclyl(R²³)_(h),—O(CH₂CH₂)N(C₁₋₃ alkyl)₂, and —O(CH₂)phenyl(R²¹)_(k).

In some embodiments, each R⁷ is one substituent attached to thepyrimidinyl and is independently selected from the group consisting ofH, halide, —(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R⁸)_(h),—(C₁₋₄ alkylene)_(p)carbocyclyl(R¹²)_(j), —(C₁₋₄alkylene)_(p)aryl(R¹³)_(k), —NHC(═O)R⁴, —NR¹⁵R¹⁶, —(C₁₋₆alkylene)NR¹⁷R¹⁸, and —OR²⁴.

In some embodiments, each R⁷ is one substituent attached to thepyrimidinyl and is independently selected from the group consisting ofhalide, —(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R⁸)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹²)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹³)_(k),—NHC(═O)R⁴, —NR¹⁵R¹⁶, —(C₁₋₆ alkylene)NR¹⁷R¹⁸, and —OR²⁴.

In some embodiments, each R⁷ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofH, —(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R⁷ is one substituent attached to theheterocyclyl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R⁸ is one substituent attached to theheteroaryl and is independently selected from the group consisting of H,—(C₁₋₆ alkyl), halide, —CF₃, —OCH₃, —CN, and —C(═O)R¹⁹.

In some embodiments, each R⁸ is one substituent attached to theheteroaryl and is independently selected from the group consisting of—(C₁₋₆ alkyl), halide, —CF₃, —OCH₃, —CN, and —C(═O)R¹⁹.

In some embodiments, each R⁸ is one substituent attached to theheteroaryl and is independently selected from the group consisting of H,-Me, -Et, F, —CF₃, —OCH₃, —CN, and —C(═O)(C₁₋₃ alkyl).

In some embodiments, each R⁸ is one substituent attached to theheteroaryl and is independently selected from the group consisting of-Me, -Et, F, —CF₃, —OCH₃, —CN, and —C(═O)(C₁₋₃ alkyl).

In some embodiments, each R⁹ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofH, —(C₁₋₆ alkyl), halide, —CF₃, —CN, and —OCH₃.

In some embodiments, each R⁹ is one substituent attached to theheterocyclyl and is independently selected from the group consisting of—(C₁₋₆ alkyl), halide, —CF₃, —CN, and —OCH₃.

In some embodiments, each R¹⁰ is one substituent attached to the aryland is independently selected from the group consisting of H, —(C₁₋₆alkyl), halide, —CF₃, —CN, —OCH₃, —(C₁₋₆ alkylene)_(p)NHSO₂R¹⁹,—NR¹⁵(C₁₋₆ alkylene)NR¹⁵R¹⁶, —(C₁₋₆ alkylene)_(p)NR¹⁵R¹⁶, and —OR²⁷.

In some embodiments, each R¹⁰ is one substituent attached to the aryland is independently selected from the group consisting of —(C₁₋₆alkyl), halide, —CF₃, —CN, —OCH₃, —(C₁₋₆ alkylene)_(p)NHSO₂R¹⁹,—NR¹⁵(C₁₋₆ alkylene)NR¹⁵R¹⁶, —(C₁₋₆ alkylene)_(p)NR¹⁵R¹⁶, and —OR²⁷.

In some embodiments, each R¹⁰ is one substituent attached to the aryland is independently selected from the group consisting of H, -Me, -Et,F, —CF₃, —CN, —OCH₃, —(CH₂CH₂)NHSO₂(C₁₋₃ alkyl), —NH(CH₂CH₂)N(C₁₋₃alkyl)₂, —OH, —O(C₁₋₃ alkyl), —O(CH₂CH₂)heterocyclyl(R²³)_(h), and—O(CH₂CH₂)N(C₁₋₃ alkyl)₂.

In some embodiments, each R¹⁰ is one substituent attached to the aryland is independently selected from the group consisting of -Me, -Et, F,—CF₃, —CN, —OCH₃, —(CH₂CH₂)NHSO₂(C₁₋₃ alkyl), —NH(CH₂CH₂)N(C₁₋₃ alkyl)₂,—OH, —O(C₁₋₃ alkyl), —O(CH₂CH₂)heterocyclyl(R²³)_(h), and—O(CH₂CH₂)N(C₁₋₃ alkyl)₂.

In some embodiments, each R¹¹ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofH, amino, —(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹¹ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofamino, —(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹¹ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofamino, Me, Et, F, Cl, and —CF₃.

In some embodiments, each R¹² is one substituent attached to thecarbocyclyl and is independently selected from the group consisting ofH, —(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹² is one substituent attached to thecarbocyclyl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹² is one substituent attached to thecarbocyclyl and is independently selected from the group consisting ofMe, Et, F, Cl, and —CF₃.

In some embodiments, each R³ is one substituent attached to the aryl andis independently selected from the group consisting of H, —(C₁₋₄ alkyl),halide, —CF₃, and —CN.

In some embodiments, each R³ is one substituent attached to the aryl andis independently selected from the group consisting of —(C₁₋₄ alkyl),halide, —CF₃, and —CN.

In some embodiments, each R³ is one substituent attached to the aryl andis independently selected from the group consisting of Me, Et, F, Cl,and —CF₃.

In some embodiments, each R¹⁴ is independently selected from the groupconsisting of —(C₁₋₉ alkyl), -heteroaryl(R²⁰)_(q), -aryl(R²¹)_(k),—CH₂aryl(R²¹)_(k), -carbocyclyl(R²²)_(j), and —CH₂carbocyclyl(R²²)_(j).

In some embodiments, each R¹⁴ is independently selected from the groupconsisting of —(C₁₋₉ alkyl), -heteroaryl(R²⁰)_(q), -aryl(R²¹)_(k),—CH₂aryl(R²¹)_(k), -carbocyclyl(R²²)_(j), —CH₂carbocyclyl(R²²)_(j),—(C₁₋₄ alkylene)_(p)NR²⁵R²⁶, -heterocyclyl(R²³)_(h), and—CH₂heterocyclyl(R²³)_(h).

In some embodiments, each R¹⁴ is independently selected from the groupconsisting of —(C₁₋₅ alkyl), -phenyl(R²¹)_(k), —(CH₂)phenyl(R²¹)_(k),-carbocyclyl(R²²)_(j), —(CH₂)carbocyclyl(R²²)_(j), —(CH₂)N(C₁₋₃ alkyl)₂,and —(CH₂)heterocyclyl(R²³)_(h).

In some embodiments, each R¹⁵ is independently selected from the groupconsisting of H and —(C₁₋₆ alkyl).

In some embodiments, each R¹⁵ is independently selected from the groupconsisting of H and —(C₁₋₃ alkyl).

In some embodiments, each R¹⁶ is independently selected from the groupconsisting of H, —(C₁₋₆ alkyl), —CH₂aryl(R²¹)_(k), and—CH₂carbocyclyl(R²²)_(j).

In some embodiments, each R¹⁶ is independently selected from the groupconsisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R²¹)_(k), and—CH₂carbocyclyl(R²²)_(j).

In some embodiments, each R¹⁷ is independently selected from the groupconsisting of H and —(C₁₋₆ alkyl).

In some embodiments, each R¹⁷ is independently selected from the groupconsisting of H and —(C₁₋₃ alkyl).

In some embodiments, each R¹⁸ is independently selected from the groupconsisting of H, —(C₁₋₆ alkyl), —CH₂aryl(R²¹)_(k), and—CH₂carbocyclyl(R²²)_(j).

In some embodiments, each R¹⁸ is independently selected from the groupconsisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R²¹)_(k), and—CH₂carbocyclyl(R²²)_(j).

In some embodiments, each R¹⁹ is independently a —(C₁₋₆ alkyl).

In some embodiments, each R¹⁹ is independently a —(C₁₋₃ alkyl).

In some embodiments, each R²⁰ is one substituent attached to theheteroaryl and is independently selected from the group consisting of H,—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R²⁰ is one substituent attached to theheteroaryl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R²⁰ is one substituent attached to theheteroaryl and is independently selected from the group consisting ofMe, Et, F, Cl, and —CF₃.

In some embodiments, each R²¹ is one substituent attached to the aryland is independently selected from the group consisting of H, —(C₁₋₄alkyl), halide, —CF₃, and —CN.

In some embodiments, each R²¹ is one substituent attached to the aryland is independently selected from the group consisting of —(C₁₋₄alkyl), halide, —CF₃, and —CN.

In some embodiments, each R²¹ is one substituent attached to the aryland is independently selected from the group consisting of Me, Et, F,Cl, and —CF₃.

In some embodiments, each R²² is one substituent attached to thecarbocyclyl and is independently selected from the group consisting ofH, —(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R²² is one substituent attached to thecarbocyclyl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R²² is one substituent attached to thecarbocyclyl and is independently selected from the group consisting ofMe, Et, F, Cl, and —CF₃.

In some embodiments, each R²³ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofH, —(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R²³ is one substituent attached to theheterocyclyl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R²³ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofMe, Et, F, Cl, and —CF₃.

In some embodiments, R²⁴ is selected from the group consisting of H,—(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R²³)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R²²)_(j), —(C₁₋₄ alkylene)_(p)aryl(R²¹)_(k),and —(C₁₋₆ alkylene)_(p)NR²⁵R²⁶.

In some embodiments, R²⁴ is selected from the group consisting of H,-Me, -Et, -iPr, -heterocyclyl(R²³)_(h), —(CH₂CH₂)heterocyclyl(R²³)_(h),-carbocyclyl(R²²)_(j), —(CH₂)phenyl(R²¹)_(k), and —(CH₂CH₂)N(C₁₋₃alkyl)₂.

In some embodiments, each R²⁵ is independently selected from the groupconsisting of H and —(C₁₋₆ alkyl).

In some embodiments, each R²⁵ is independently selected from the groupconsisting of Me and Et.

In some embodiments, each R²⁶ is independently selected from the groupconsisting of H and —(C₁₋₆ alkyl).

In some embodiments, each R²⁶ is independently selected from the groupconsisting of Me and Et.

In some embodiments, R²⁷ is selected from the group consisting of H,—(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R²³)_(h), and —(C₁₋₆alkylene)_(p)NR²⁵R²⁶.

In some embodiments, R²⁷ is selected from the group consisting of H,-Me, -Et, -iPr, —(CH₂CH₂)heterocyclyl(R²³)_(h), and —(CH₂CH₂)N(C₁-3alkyl)₂.

In some embodiments, each p is independently 0 or 1; in someembodiments, each p is 0; in some embodiments, each p is 1.

In some embodiments, each q is independently 0 to 4; in someembodiments, each q is 0; in some embodiments, each q is 1; in someembodiments, each q is 2; in some embodiments, each q is 3; in someembodiments, each q is 4.

In some embodiments, each h is independently 0 to 10; in someembodiments, each h is 0; in some embodiments, each h is 1; in someembodiments, each h is 2; in some embodiments, each h is 3; in someembodiments, each h is 4.

In some embodiments, each k is independently 0 to 5; in someembodiments, each k is 0; in some embodiments, each k is 1; in someembodiments, each k is 2; in some embodiments, each k is 3.

In some embodiments, each j is independently 0 to 12; in someembodiments, each j is 0; in some embodiments, each j is 1; in someembodiments, each j is 2; in some embodiments, each j is 3; in someembodiments, each j is 4.

In some embodiments, each R⁶ is one substituent attached to theheteroaryl and is independently selected from the group consisting of—(C₁₋₃ alkyl), —CH₂heterocyclyl(R¹¹)_(h), —NHC(═O)R¹⁴, —NR¹⁵R¹⁶, and—CH₂NR¹⁷R¹⁸.

In some embodiments, at least one R¹¹ is halide.

In some embodiments, R¹⁴ is selected from the group consisting of —(C₁₋₅alkyl), -phenyl(R²¹)_(k), —CH₂phenyl(R²¹)_(k), and-carbocyclyl(R²²)_(j).

In some embodiments, each R¹⁵ and R¹⁶ are independently selected from Hand —(C₁₋₅ alkyl).

In some embodiments, each R¹⁷ and R¹⁸ are independently selected from Hand —(C₁₋₅ alkyl).

In some embodiments, k is 1 or 2 and each R¹⁰ is independently a halide.

In some embodiments, k is 2 and one R¹⁰ is halide and the other R¹⁰ is—CH₂NHSO₂R⁹.

In some embodiments, R¹⁹ is —(C₁₋₃ alkyl).

In some embodiments, k is 2 and one R¹⁰ is halide and the other R¹⁰ is—NHCH₂CH₂NR¹⁵R¹⁶.

In some embodiments, each R¹⁵ and R¹⁶ are independently selected from Hand —(C₁₋₃ alkyl).

In some embodiments, R⁵ is selected from the group consisting of-pyridinyl(R⁸)_(q), -imidazolyl(R⁸)_(q), -furanyl(R⁸)_(q), and-thiophenyl(R⁸)_(q).

In some embodiments, q is 0 or 1, and R⁸ is selected from the groupconsisting of halide, —(C₁₋₃ alkyl), —C(═O)R¹⁹, wherein R¹⁹ is —(C₁₋₂alkyl).

In some embodiments, R⁵ is selected from the group consisting of-piperidinyl(R⁹)_(h) and -piperazinyl(R⁹)_(h).

In some embodiments, q is 1, and R⁹ is selected from the groupconsisting of H and —(C₁₋₃ alkyl).

In some embodiments, R¹ is H; in other embodiments, R¹ is halide, e.g.F.

In some embodiments, R² is H; in other embodiments, R² is halide, e.g.F.

In some embodiments, R⁴ is H; in other embodiments, R⁴ is halide, e.g.F.

In some embodiments, R² and R⁴ are H, and R¹ is F; in some embodiments,R¹ and R⁴ are H, and R² is F; in some embodiments, R¹ and R² are H, andR⁴ is F; in some embodiments, R² and R⁴ are F, and R¹ is H; in someembodiments, R¹ and R⁴ are F, and R² is H; in some embodiments, R¹ andR² are F, and R⁴ is H; in some embodiments, R¹, R², and R⁴ are H; insome embodiments, R¹, R², and R⁴ are F.

In some embodiments, R³ is -heteroaryl(R⁶)_(q).

In some embodiments, R³ is -pyridinyl(R⁶)_(q).

In some embodiments, R³ is -pyridin-3-yl(R⁶)_(q).

In some embodiments, R³ is -pyrimidinyl(R⁶)_(q).

In some embodiments, R³ is -pyrimidin-5-yl(R⁶)_(q).

In some embodiments, R³ is -pyrimidin-5-yl(R⁶)_(q) and q is 0.

In some embodiments, R³ is -pyrazinyl(R⁶)_(q).

In some embodiments, R³ is -pyrazolyl(R⁶)_(q).

In some embodiments, R³ is -pyrazol-4-yl(R⁶)_(q), q is 1, and R⁶ is Me.

In some embodiments, R³ is -pyrazol-4-yl(R⁶)_(q) and q is 0.

In some embodiments, R³ is -imidazolyl(R⁶)_(q).

In some embodiments, R³ is -imidazol-5-yl(R⁶)_(q), q is 1, and R⁶ is Me.

In some embodiments, R³ is -imidazol-5-yl(R⁶)_(q), q is 2, and both R⁶are Me.

In some embodiments, R³ is -heterocyclyl(R⁷)_(h).

In some embodiments, R³ is -piperidinyl(R⁷)_(h).

In some embodiments, R³ is -piperidin-4-yl(R⁷)_(h).

In some embodiments, R³ is -piperidin-4-yl(R⁷)_(h), and h is 0.

In some embodiments, R³ is -tetrahydropyridinyl(R⁷)_(h).

In some embodiments, R³ is -1,2,3,6-tetrahydropyridinyl(R⁷)_(h).

In some embodiments, R³ is -1,2,3,6-tetrahydropyridinyl(R⁷)_(h), and his 0.

In some embodiments, R⁵ is H.

In some embodiments, R⁵ is -heteroaryl(R⁸)_(q).

In some embodiments, R⁵ is -heterocyclyl(R⁹)_(h).

In some embodiments, R⁵ is -piperidinyl(R⁹)_(h).

In some embodiments, R⁵ is -piperazinyl(R⁹)_(h).

In some embodiments, R⁵ is -aryl(R¹⁰)_(k).

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k).

In some embodiments, R⁵ is -pyridinyl(R⁸)_(q).

In some embodiments, R⁵ is -pyridin-3-yl(R⁸)_(q).

In some embodiments, R⁵ is -pyridin-4-yl(R⁸)_(q).

In some embodiments, R⁵ is -pyridin-5-yl(R⁸)_(q).

In some embodiments, R⁵ is -pyridin-3-yl(R⁸)_(q) and q is 0.

In some embodiments, R⁵ is -pyridin-4-yl(R⁸)_(q) and q is 0.

In some embodiments, R⁵ is -pyridin-5-yl(R⁸)_(q) and q is 0.

In some embodiments, R⁵ is -imidazolyl(R⁸)_(q).

In some embodiments, R⁵ is -imidazol-1-yl(R⁸)_(q), q is 1, and R⁸ is—(C₁₋₃ alkyl).

In some embodiments, R⁵ is -imidazol-1-yl(R⁸)_(q), q is 1, and R⁸ ismethyl.

In some embodiments, R⁵ is -furanyl(R⁸)_(q).

In some embodiments, R⁵ is -furan-2-yl(R⁸)_(q).

In some embodiments, R⁵ is -furan-2-yl(R⁸)_(q) and q is 0.

In some embodiments, R⁵ is -furan-3-yl(R⁸)_(q).

In some embodiments, R⁵ is -furan-3-yl(R⁸)_(q) and q is 0.

In some embodiments, R⁵ is -thiophenyl(R⁸)_(q).

In some embodiments, R⁵ is -thiophen-2-yl(R⁸)_(q).

In some embodiments, R⁵ is -thiophen-2-yl(R⁸)_(q) and q is 0.

In some embodiments, R⁵ is -thiophen-2-yl(R⁸)_(q), q is 1 or 2, and eachR⁸ is independently a halide.

In some embodiments, R⁵ is -thiophen-2-yl(R⁸)_(q), q is 1 or 2, and R⁸is F.

In some embodiments, R⁵ is -thiophen-2-yl(R⁸)_(q), q is 1 or 2, and eachR⁸ is independently a —(C₁₋₆ alkyl).

In some embodiments, R⁵ is -thiophen-2-yl(R⁸)_(q), q is 1 or 2, and eachR⁸ is independently a —(C₁₋₂ alkyl).

In some embodiments, R⁵ is -thiophen-2-yl(R⁸)_(q), q is 1 or 2, and R⁸is methyl.

In some embodiments, R⁵ is -thiophen-2-yl(R⁸)_(q), q is 1 or 2, and R⁸is —CF₃.

In some embodiments, R⁵ is -thiophen-2-yl(R⁸)_(q), q is 1 or 2, and R⁸is CN.

In some embodiments, R⁵ is -thiophen-2-yl(R⁸)_(q), q is 1, and R⁸ is—C(═O)R¹⁹.

In some embodiments, R⁵ is -thiophen-2-yl(R⁸)_(q), q is 1, R⁸ is—C(═O)R¹⁹, and R¹⁹ is —(C₁₋₆ alkyl).

In some embodiments, R⁵ is -thiophen-2-yl(R⁸)_(q), q is 1, R⁸ is—C(═O)R¹⁹, and R¹⁹ is —(C₁₋₄ alkyl).

In some embodiments, R⁵ is -thiophen-2-yl(R⁸)_(q), q is 1, R⁸ is—C(═O)R¹⁹, and R¹⁹ is —(C₁₋₂ alkyl).

In some embodiments, R⁵ is -thiophen-2-yl(R⁸)_(q), q is 1, R⁸ is—C(═O)R¹⁹, and R¹⁹ is methyl.

In some embodiments, R⁵ is -thiophen-3-yl(R⁸)_(q).

In some embodiments, R⁵ is -thiophen-3-yl(R⁸)_(q) and q is 0.

In some embodiments, R⁵ is -thiophen-3-yl(R⁸)_(q), q is 1 or 2, and eachR⁸ is independently a halide.

In some embodiments, R⁵ is -thiophen-3-yl(R⁸)_(q), q is 1 or 2, and R⁸is F.

In some embodiments, R⁵ is -thiophen-3-yl(R⁸)_(q), q is 1 or 2, and eachR⁸ is independently a —(C₁₋₆ alkyl).

In some embodiments, R⁵ is -thiophen-3-yl(R⁸)_(q), q is 1 or 2, and eachR⁸ is independently a —(C₁₋₂ alkyl).

In some embodiments, R⁵ is -thiophen-3-yl(R⁸)_(q), q is 1 or 2, and R⁸is methyl.

In some embodiments, R⁵ is -thiophen-3-yl(R⁸)_(q), q is 1 or 2, and R⁸is —CF₃.

In some embodiments, R⁵ is -thiophen-3-yl(R⁸)_(q), q is 1 or 2, and R⁸is CN.

In some embodiments, R⁵ is -thiophen-3-yl(R⁸)_(q), q is 1, and R⁸ is—C(═O)R¹⁹.

In some embodiments, R⁵ is -thiophen-3-yl(R⁸)_(q), q is 1, R⁸ is—C(═O)R¹⁹, and R¹⁹ is —(C₁₋₄ alkyl).

In some embodiments, R⁵ is -thiophen-3-yl(R⁸)_(q), q is 1, R⁸ is—C(═O)R¹⁹, and R¹⁹ is —(C₁₋₂ alkyl).

In some embodiments, R⁵ is -thiophen-3-yl(R⁸)_(q), q is 1, R⁸ is—C(═O)R¹⁹, and R¹⁹ is methyl.

In some embodiments, R⁵ is selected from the group consisting of:

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k).

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k) and k is 0.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 1 or 2, and each R¹⁰is independently a halide.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 1 or 2, and R¹⁰ is F.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 1, and R¹⁰ is F.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is a halideand the other R¹⁰ is —(C₁₋₆ alkylene)_(p)NHSO₂R¹⁹.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is a halideand the other R¹⁰ is —(C₁₋₄ alkylene)_(p)NHSO₂R¹⁹, and p is 1.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is a halideand the other R¹⁰ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁹, and p is 1.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is a halideand the other R¹⁰ is —CH₂NHSO₂R¹⁹.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is a halideand the other R¹⁰ is —CH₂NHSO₂R¹⁹, and R¹⁹ is —(C₁₋₄ alkyl).

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is a halideand the other R¹⁰ is —CH₂NHSO₂R¹⁹, and R¹⁹ is —(C₁₋₂ alkyl).

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is a halideand the other R¹⁰ is —CH₂NHSO₂R¹⁹, and R¹⁹ is methyl.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is F andthe other R¹⁰ is —CH₂NHSO₂R¹⁹, and R¹⁹ is —(C₁₋₂ alkyl).

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is F andthe other R¹⁰ is —CH₂NHSO₂R¹⁹, and R¹⁹ is methyl.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is halideand the other R¹⁰ is —NR¹⁵(C₁₋₆ alkylene)NR¹⁵R¹⁶.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is halideand the other R¹⁰ is —NR¹⁵(C₁₋₅ alkylene)NR¹⁵R¹⁶.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is halideand the other R¹⁰ is —NR¹⁵(C₁₋₄ alkylene)NR¹⁵R¹⁶.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is halideand the other R¹⁰ is —NR¹⁵(C₁₋₃ alkylene)NR¹⁵R¹⁶.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is halideand the other R¹⁰ is —NR¹⁵CH₂CH₂NR¹⁵R¹⁶.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is halideand the other R¹⁰ is —NHCH₂CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ are independentlya —(C₁₋₆ alkyl).

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is halideand the other R¹⁰ is —NHCH₂CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ are independentlya —(C₁₋₄ alkyl).

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is halideand the other R¹⁰ is —NHCH₂CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ are independentlya —(C₁₋₂ alkyl).

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is halideand the other R¹⁰ is —NHCH₂CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ are both methyl.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is F andthe other R¹⁰ is —NHCH₂CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ are independently a—(C₁₋₂ alkyl).

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is F andthe other R¹⁰ is —NHCH₂CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ are both methyl.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is halideand the other R¹⁰ is —OCH₂CH₂NR²⁵R²⁶.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is halideand the other R¹⁰ is —OCH₂CH₂NR²⁵R²⁶, and R²⁵ and R²⁶ are independentlya —(C₁₋₂ alkyl).

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is halideand the other R¹⁰ is —OCH₂CH₂NR²⁵R²⁶, and R²⁵ and R²⁶ are both methyl.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is F andthe other R¹⁰ is —OCH₂CH₂NR²⁵R²⁶, and R²⁵ and R²⁶ are both methyl.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is halideand the other R¹⁰ is —CH₂NHSO₂R¹⁹, and R¹⁹ is —(C₁₋₄ alkyl).

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is halideand the other R¹⁰ is —CH₂NHSO₂R¹⁹, and R¹⁹ is —(C₁₋₂ alkyl).

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is halideand the other R¹⁰ is —CH₂NHSO₂R¹⁹, and R¹⁹ is methyl.

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is F andthe other R¹⁰ is —CH₂NHSO₂R¹⁹, and R¹⁹ is —(C₁₋₂ alkyl).

In some embodiments, R⁵ is -phenyl(R¹⁰)_(k), k is 2, one R¹⁰ is F andthe other R¹⁰ is —CH₂NHSO₂R¹⁹, and R¹⁹ is methyl.

In some embodiments, R⁵ is selected from the group consisting of:

In some embodiments, R⁵ is -piperidinyl(R⁹)_(h).

In some embodiments, R⁵ is -piperidin-1-yl(R⁹)_(h).

In some embodiments, R⁵ is -piperidin-1-yl(R⁹)_(h) and h is 0.

In some embodiments, R⁵ is -piperidin-1-yl(R⁹)_(h), h is 1 or 2, andeach R⁹ is independently selected from a halide.

In some embodiments, R⁵ is -piperazinyl(R⁹)_(h).

In some embodiments, R⁵ is -piperazin-1-yl(R⁹)_(h).

In some embodiments, R⁵ is -piperazin-1-yl(R⁹)_(h), h is 1, and R⁹ isC₁₋₃ alkyl.

In some embodiments, R⁵ is -piperazin-1-yl(R⁹)_(h), h is 1, and R⁹ ismethyl.

In some embodiments, R⁵ is -morpholinyl(R⁹)_(h).

In some embodiments, R⁵ is -morpholin-1-yl(R⁹)_(h).

In some embodiments, R⁵ is -morpholin-1-yl(R⁹)_(h) and h is 0.

In some embodiments, R⁵ is selected from the group consisting of:

In some embodiments, q is 0.

In some embodiments, at least one R⁶ is a halide.

In some embodiments, at least one R⁶ is a F.

In some embodiments, R⁶ is F.

In some embodiments, at least one R⁶ is —(C₁₋₆ alkyl).

In some embodiments, at least one R⁶ is —(C₁₋₅ alkyl).

In some embodiments, at least one R⁶ is —(C₁₋₄ alkyl).

In some embodiments, at least one R⁶ is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁶ is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁶ is methyl.

In some embodiments, R⁶ is a methyl.

In some embodiments, at least one R⁶ is —(C₁₋₄alkylene)_(p)heterocyclyl(R¹¹)_(h) and p is 0 or 1.

In some embodiments, at least one R⁶ is —(C₁₋₃alkylene)_(p)heterocyclyl(R¹¹)_(h) and p is 0 or 1.

In some embodiments, at least one R⁶ is —(C₁₋₂alkylene)_(p)heterocyclyl(R¹¹)_(h) and p is 0 or 1.

In some embodiments, at least one R⁶ is —CH₂pyrrolidinyl(R¹¹)_(h).

In some embodiments, at least one R⁶ is —CH₂pyrrolidinyl(R¹¹)_(h) and his 0.

In some embodiments, R⁶ is a —CH₂pyrrolidinyl(R¹¹)_(h) and h is 0.

In some embodiments, at least one R⁶ is —CH₂pyrrolidinyl(R¹¹)_(h), h is1 or 2, and at least one R¹¹ is a halide.

In some embodiments, at least one R⁶ is —CH₂pyrrolidinyl(R¹¹)_(h), h is1 or 2, and at least one R¹¹ is F.

In some embodiments, R⁶ is a —CH₂pyrrolidinyl(R¹¹)_(h), h is 1 or 2, andat least one R¹¹ is halide.

In some embodiments, R⁶ is —CH₂pyrrolidinyl(R¹¹)_(h), h is 1 or 2, andat least one R¹¹ is F.

In some embodiments, R⁶ is a —CH₂pyrrolidinyl(R¹¹)_(h), h is 1 or 2, andeach R¹¹ is F.

In some embodiments, at least one R⁶ is —CH₂piperidinyl(R¹¹)_(h).

In some embodiments, at least one R⁶ is —CH₂piperidinyl(R¹¹)_(h) and his 0.

In some embodiments, R⁶ is a —CH₂piperidinyl(R¹¹)_(h) and h is 0.

In some embodiments, at least one R⁶ is —CH₂piperidinyl(R¹¹)_(h) and atleast one R¹¹ is a halide.

In some embodiments, at least one R⁶ is —CH₂piperidinyl(R¹¹)_(h) and atleast one R¹¹ is F.

In some embodiments, at least one R⁶ is —CH₂piperidinyl(R¹¹)_(h), h is 1or 2, and each R¹¹ is a halide.

In some embodiments, at least one R⁶ is —CH₂piperidinyl(R¹¹)_(h), h is 1or 2, and each R¹¹ is F.

In some embodiments, R⁶ is —CH₂piperidinyl(R¹¹)_(h), h is 1 or 2, andeach R¹¹ is a halide.

In some embodiments, R⁶ is a —CH₂piperidinyl(R¹¹)_(h), h is 1 or 2, andeach R¹¹ is F.

In some embodiments, R⁶ is a

In some embodiments, at least one R⁶ is —(C₁₋₄alkylene)_(p)carbocyclyl(R¹²)_(j).

In some embodiments, at least one R⁶ is —(C₁₋₄alkylene)_(p)carbocyclyl(R¹²)_(j) and j is 0 or 1.

In some embodiments, at least one R⁶ is —(C₁₋₃alkylene)_(p)carbocyclyl(R¹²)_(j) and j is 0 or 1.

In some embodiments, at least one R⁶ is —(C₁₋₂alkylene)_(p)carbocyclyl(R¹²)_(j) and j is 0 or 1.

In some embodiments, at least one R⁶ is —CH₂carbocyclyl(R¹²)_(j).

In some embodiments, R⁶ is a —CH₂carbocyclyl(R¹²)_(j).

In some embodiments, at least one R⁶ is —(C₁₋₄alkylene)_(p)aryl(R¹³)_(k) and k is 0 or 1.

In some embodiments, at least one R⁶ is —(C₁₋₃alkylene)_(p)aryl(R¹³)_(k) and k is 0 or 1.

In some embodiments, at least one R⁶ is —(C₁₋₂alkylene)_(p)aryl(R¹³)_(k) and k is 0 or 1.

In some embodiments, at least one R⁶ is —CH₂aryl(R¹³)_(k).

In some embodiments, at least one R⁶ is —CH₂phenyl(R³)_(k).

In some embodiments, R⁶ is a —CH₂phenyl(R¹³)_(k).

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴.

In some embodiments, R⁶ is a —NHC(═O)R¹⁴.

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴ and R¹⁴ is —(C₁₋₉alkyl).

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴ and R¹⁴ is —(C₁₋₈alkyl).

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴ and R¹⁴ is —(C₁₋₇alkyl).

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴ and R¹⁴ is —(C₁₋₆alkyl).

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴ and R¹⁴ is —(C₁₋₅alkyl).

In some embodiments, R⁶ is a —NHC(═O)R¹⁴ and R¹⁴ is —(C₁₋₅ alkyl).

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴ and R¹⁴ is —(C₁₋₄alkyl).

In some embodiments, R⁶ is a —NHC(═O)R¹⁴ and R¹⁴ is —(C₁₋₄ alkyl).

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴ and R¹⁴ is —(C₁₋₃alkyl).

In some embodiments, R⁶ is a —NHC(═O)R¹⁴ and R¹⁴ is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴ and R¹⁴ is —(C₁₋₂alkyl).

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴ and R¹⁴ is —(C₂₋₅alkyl).

In some embodiments, R⁶ is a —NHC(═O)R¹⁴ and R¹⁴ is —(C₂₋₅ alkyl).

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴ and R¹⁴ is —(C₃₋₄alkyl).

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴ and R¹⁴ is-aryl(R²¹)_(k).

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴, R¹⁴ is-phenyl(R²¹)_(k), and k is 0.

In some embodiments, R⁶ is a —NHC(═O)R¹⁴, R¹⁴ is -phenyl(R²¹)_(k), and kis 0.

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴ and R¹⁴ is—CH₂aryl(R²¹)_(k).

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴, R¹⁴ is—CH₂phenyl(R²¹)_(k), and k is 0.

In some embodiments, R⁶ is a —NHC(═O)R¹⁴, R¹⁴ is —CH₂phenyl(R²¹)_(k),and k is 0.

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴ and R¹⁴ is-heteroaryl(R²⁰)_(q).

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴ and R¹⁴ is-carbocyclyl(R²²)_(j).

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴, R¹⁴ is-carbocyclyl(R²²)_(j), and j is 0.

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴, R¹⁴ is-cyclopropyl(R²²)_(j), and j is 0.

In some embodiments, R⁶ is a —NHC(═O)R¹⁴, R¹⁴ is -cyclopropyl(R²²), andj is 0.

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴, R¹⁴ is-cyclobutyl(R²²)_(j), and j is 0.

In some embodiments, R⁶ is a —NHC(═O)R¹⁴, R¹⁴ is -cyclobutyl(R¹²)_(j),and j is 0.

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴, R¹⁴ is-cyclopentyl(R²²)_(j), and j is 0.

In some embodiments, R⁶ is a —NHC(═O)R¹⁴, R¹⁴ is -cyclopentyl(R²²)_(j),and j is 0.

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴, R¹⁴ is-cyclohexyl(R²²)_(j), and j is 0.

In some embodiments, R⁶ is a —NHC(═O)R¹⁴, R¹⁴ is -cyclohexyl(R²²)_(j),and j is 0.

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴, R¹⁴ is—CH₂carbocyclyl(R²²)_(j), and j is 0.

In some embodiments, at least one R⁶ is —NHC(═O)R¹⁴, R¹⁴ is—CH₂cyclopropyl(R²²)_(j), and j is 0.

In some embodiments, R⁶ is a —NHC(═O)R¹⁴, R¹⁴ is—CH₂cyclopropyl(R²²)_(j), and j is 0.

In some embodiments, at least one R⁶ is —NR¹⁵R¹⁶.

In some embodiments, at least one R⁶ is —NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and —(C₁₋₆ alkyl).

In some embodiments, at least one R⁶ is —NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and —(C₁₋₅ alkyl).

In some embodiments, at least one R⁶ is —NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and —(C₁₋₄ alkyl).

In some embodiments, at least one R⁶ is —NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and —(C₁₋₃ alkyl).

In some embodiments, at least one R⁶ is —NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and —(C₁₋₂ alkyl).

In some embodiments, at least one R⁶ is —NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and methyl.

In some embodiments, R⁶ is a —NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ are independentlyselected from the group consisting of H and methyl.

In some embodiments, at least one R⁶ is —NH₂.

In some embodiments, R⁶ is a —NH₂.

In some embodiments, at least one R⁶ is —NHR¹⁶ and R¹⁶ is —(C₁₋₄ alkyl).

In some embodiments, at least one R⁶ is —NHR¹⁶ and R¹⁶ is —(C₁₋₃ alkyl).

In some embodiments, R⁶ is —NHR¹⁶ and R¹⁶ is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁶ is —NHR¹⁶ and R¹⁶ is—CH₂aryl(R²¹)_(k).

In some embodiments, R⁶ is —NHR¹⁶, R¹⁶ is —CH₂phenyl(R²¹)_(k), and k is0.

In some embodiments, at least one R⁶ is —NHR¹⁶ and R¹⁶ is—CH₂carbocyclyl(R²²)_(j).

In some embodiments, at least one R⁶ is —NHR¹⁶, R¹⁶ is—CH₂cyclopropyl(R²²)_(j), and j is 0.

In some embodiments, R⁶ is a —NHR¹⁶, R¹⁶ is —CH₂cyclopropyl(R²²)_(j),and j is 0.

In some embodiments, at least one R⁶ is —NHR¹⁶, R¹⁶ is—CH₂cyclobutyl(R²²)_(j), and j is 0.

In some embodiments, R⁶ is a —NHR¹⁶, R¹⁶ is —CH₂cyclobutyl(R²²)_(j), andj is 0.

In some embodiments, at least one R⁶ is —NHR¹⁶, R¹⁶ is—CH₂cyclopentyl(R²²)_(j), and j is 0.

In some embodiments, R⁶ is a —NHR¹⁶, R¹⁶ is —CH₂cyclopentyl(R²²)_(j),and j is 0.

In some embodiments, at least one R⁶ is —NHR¹⁶, R¹⁶ is—CH₂cyclohexyl(R²²)_(j), and j is 0.

In some embodiments, R⁶ is a —NHR¹⁶, R¹⁶ is —CH₂cyclohexyl(R²²)_(j), andj is 0.

In some embodiments, at least one R⁶ is —(C₁₋₆ alkylene)NR¹⁷R¹⁸.

In some embodiments, at least one R⁶ is —(C₁₋₅ alkylene)NR¹⁷R¹⁸.

In some embodiments, at least one R⁶ is —(C₁₋₄ alkylene)NR¹⁷R¹⁸.

In some embodiments, at least one R⁶ is —(C₁₋₃ alkylene)NR¹⁷R¹⁸.

In some embodiments, at least one R⁶ is —(C₁₋₂ alkylene)NR¹⁷R¹⁸.

In some embodiments, at least one R⁶ is —CH₂NR¹⁷R¹⁸.

In some embodiments, R⁶ is a —CH₂NR¹⁷R¹⁸.

In some embodiments, at least one R⁶ is —CH₂NR¹⁷R¹⁸, and R⁷ and R¹⁸ areindependently selected from the group consisting of H and —(C₁₋₆ alkyl).

In some embodiments, at least one R⁶ is —CH₂NR¹⁷R¹⁸, and R⁷ and R¹⁸ areindependently selected from the group consisting of H and —(C₁₋₅ alkyl).

In some embodiments, at least one R⁶ is —CH₂NR¹⁷R¹⁸, and R¹⁷ and R¹⁸ areindependently selected from the group consisting of H and —(C₁₋₄ alkyl).

In some embodiments, at least one R⁶ is —CH₂NR¹⁷R¹⁸, and R¹⁷ and R¹⁸ areindependently selected from the group consisting of H and —(C₁₋₃ alkyl).

In some embodiments, at least one R⁶ is —CH₂NR¹⁷R¹⁸, and R⁷ and R¹⁸ areindependently selected from the group consisting of H and —(C₁₋₂ alkyl).

In some embodiments, at least one R⁶ is —CH₂NR¹⁷R¹⁸, and R⁷ and R¹⁸ areindependently selected from the group consisting of H and methyl.

In some embodiments, R⁶ is a —CH₂NR¹⁷R¹⁸, and R¹⁷ and R¹⁸ areindependently selected from the group consisting of H and methyl.

In some embodiments, at least one R⁶ is —CH₂NH₂.

In some embodiments, R⁶ is a —CH₂NH₂.

In some embodiments, at least one R⁶ is —CH₂NMe₂.

In some embodiments, R⁶ is a —CH₂NMe₂.

In some embodiments, at least one R⁶ is —CH₂NHR¹⁸ and R¹⁸ is —(C₁₋₄alkyl).

In some embodiments, at least one R⁶ is —CH₂NHR¹⁸ and R¹⁸ is —(C₁₋₃alkyl).

In some embodiments, at least one R⁶ is —CH₂NHR¹⁸ and R¹⁸ is —(C₁₋₂alkyl).

In some embodiments, R⁶ is a —CH₂NHR¹⁸ and R¹⁸ is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁶ is —CH₂NHR¹⁸ and R¹⁸ is—CH₂aryl(R²¹)_(k).

In some embodiments, at least one R⁶ is —CH₂NHR¹⁸, R¹⁸ is—CH₂phenyl(R²¹)_(k), and k is 0.

In some embodiments, R⁶ is a —CH₂NHR¹⁸, R¹⁸ is —CH₂phenyl(R²¹)_(k), andk is 0.

In some embodiments, at least one R⁶ is —CH₂NHR¹⁸ and R¹⁸ is—CH₂carbocyclyl(R²²)_(j).

In some embodiments, at least one R⁶ is —CH₂NHR¹⁸, R¹⁸ is—CH₂cyclopropyl(R²²)_(j), and j is 0.

In some embodiments, R⁶ is a —CH₂NHR¹⁸, R¹⁸ is —CH₂cyclopropyl(R²²)_(j),and j is 0.

In some embodiments, at least one R⁶ is —CH₂NHR¹⁸, R¹⁸ is—CH₂cyclobutyl(R²²)_(j), and j is 0.

In some embodiments, R⁶ is a —CH₂NHR¹⁸, R¹⁸ is —CH₂cyclobutyl(R²²)_(j),and j is 0.

In some embodiments, at least one R⁶ is —CH₂NHR¹⁸, R¹⁸ is—CH₂cyclopentyl(R²²)_(j), and j is 0.

In some embodiments, R⁶ is a —CH₂NHR¹⁸, R¹⁸ is —CH₂cyclopentyl(R²²)_(j),and j is 0.

In some embodiments, at least one R⁶ is —CH₂NHR¹⁸, R¹⁸ is—CH₂cyclohexyl(R²²), and j is 0.

In some embodiments, R⁶ is a —CH₂NHR¹⁸, R¹⁸ is —CH₂cyclohexyl(R²²)_(j),and j is 0.

In some embodiments, at least one R⁶ is —OR²⁴.

In some embodiments, at least one R⁶ is —OH.

In some embodiments, R⁶ is a —OH.

In some embodiments, at least one R⁶ is —OR²⁴ and R²⁴ is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁶ is —OR²⁴ and R²⁴ is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁶ is —OMe.

In some embodiments, R⁶ is a —OMe.

In some embodiments, at least one R⁶ is —OR²⁴, R²⁴ is-heterocyclyl(R²³)_(h), and h is 0.

In some embodiments, R⁶ is a —OR²⁴, R²⁴ is -heterocyclyl(R²³)_(h), and his 0.

In some embodiments, at least one R⁶ is —OR²⁴, R²⁴ is-carbocyclyl(R²²)_(j), and j is 0.

In some embodiments, R⁶ is a —OR²⁴, R²⁴ is -carbocyclyl(R²²)_(j), and jis 0.

In some embodiments, at least one R⁶ is —OR²⁴, R²⁴ is —(C₁₋₄alkylene)heterocyclyl(R²³)_(h), and h is 0.

In some embodiments, at least one R⁶ is —OR²⁴, R²⁴ is—(CH₂CH₂)heterocyclyl(R²³)_(h), and h is 0.

In some embodiments, R⁶ is a —OR²⁴, R²⁴ is—(CH₂CH₂)heterocyclyl(R²³)_(h), and h is 0.

In some embodiments, at least one R⁶ is —OR²⁴, R²⁴ is —(C₁₋₄alkylene)NR²⁵R²⁶ and R²⁵ and R²⁶ are independently a —(C₁₋₄ alkyl).

In some embodiments, at least one R⁶ is —OR²⁴, R²⁴ is —(CH₂CH₂)NR²⁵R²⁶and R²⁵ and R²⁶ are independently a —(C₁₋₂ alkyl).

In some embodiments, at least one R⁶ is —OR²⁴, and R²⁴ is —(CH₂CH₂)NMe₂.

In some embodiments, R⁶ is a —OR²⁴, and R²⁴ is —(CH₂CH₂)NMe₂.

In some embodiments, at least one R⁶ is —OR²⁴, R²⁴ is —(C₁₋₄alkylene)aryl(R²¹)_(k), k is 0 or 1 and R²¹ is halide.

In some embodiments, at least one R⁶ is —OR²⁴, R²⁴ is—(CH₂CH₂)phenyl(R²¹)_(k), k is 0 or 1 and R²¹ is a halide.

In some embodiments, R⁶ is a —OR²⁴, R²⁴ is —(CH₂CH₂)phenyl(R²¹)_(k), kis 0 or 1 and R²¹ is a halide.

In some embodiments, at least one R⁶ is —OR²⁴, R²⁴ is—(CH₂)phenyl(R²¹)_(k), k is 0 or 1 and R²¹ is a halide.

In some embodiments, R⁶ is a —OR²⁴, R²⁴ is —(CH₂)phenyl(R²¹)_(k), k is 0or 1 and R²¹ is a halide.

In some embodiments, h is 0.

In some embodiments, at least one R⁷ is a halide.

In some embodiments, at least one R⁷ is a F.

In some embodiments, at least one R⁷ is —(C₁₋₆ alkyl).

In some embodiments, at least one R⁷ is —(C₁₋₅ alkyl).

In some embodiments, at least one R⁷ is —(C₁₋₄ alkyl).

In some embodiments, at least one R⁷ is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁷ is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁷ is methyl.

In some embodiments, at least one R⁸ is a halide.

In some embodiments, at least one R⁸ is a F.

In some embodiments, at least one R⁸ is —(C₁₋₄ alkyl).

In some embodiments, at least one R⁸ is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁸ is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁸ is methyl.

In some embodiments, R⁸ is a methyl.

In some embodiments, at least one R⁸ is —C(═O)(C₁₋₃ alkyl).

In some embodiments, at least one R⁸ is —C(═O)Me.

In some embodiments, R⁸ is a —C(═O)Me.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is —(C₂₋₅ alkyl); R⁵ is -phenyl(R¹⁰)_(k);k is 1 or 2; and R¹⁰ is F.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is —(C₂₋₅ alkyl); R⁵ is -phenyl(R¹⁰)_(k);k is 2; one R¹⁰ is F and the other R¹⁰ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁹;p is 1; and R¹⁹ is —(C₁₋₃ alkyl).

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is —(C₂₋₅ alkyl); R⁵ is -phenyl(R¹⁰)_(k);k is 2; one R¹⁰ is F and the other R¹⁰ is —NH(C₁₋₆ alkylene)NR¹⁵R¹⁶; andR¹⁵ and R¹⁶ are independently selected from —(C₁₋₃ alkyl).

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q),wherein q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is —(C₂₋₅ alkyl); R⁵ is-heteroaryl(R⁸)_(q), wherein q is 1; R⁸ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁹; R¹⁹ is —(C₁₋₃alkyl); and the heteroaryl is selected from the group consisting ofpyridine, furan, thiophene, and imidazole.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is —(C₂₋₅ alkyl); R⁵ is-heterocyclyl(R⁹)_(h); h is 1 or 2; and R⁹ is selected from the groupconsisting of halide and —(C₁₋₂ alkyl).

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is -carbocyclyl(R²²)_(j); j is 0; R⁵ is-phenyl(R¹⁰)_(k); k is 1 or 2; R¹⁰ is F; and the carbocyclyl is selectedfrom the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is -carbocyclyl(R²²)_(j); j is 0; R⁵ is-phenyl(R¹⁰)_(k); k is 2; one R¹⁰ is F and the other R¹⁰ is —(C₁₋₂alkylene)_(p)NHSO₂R¹⁹; p is 1; R¹⁹ is —(C₁₋₃ alkyl); and the carbocyclylis selected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, and cyclohexyl.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is -carbocyclyl(R²²)_(j); j is 0; R⁵ is-phenyl(R¹⁰)_(k); k is 2; one R¹⁰ is F and the other R¹⁰ is —NH(C₁₋₆alkylene)NR¹⁵R¹⁶; R¹⁵ and R¹⁶ are independently selected from —(C₁₋₃alkyl); and the carbocyclyl is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q),wherein q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is -carbocyclyl(R²²)_(j); j is 0;R⁵ is -heteroaryl(R⁸)_(q), wherein q is 1; R⁸ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁹; R¹⁹ is C₁₋₃ alkyl;the heteroaryl is selected from the group consisting of pyridine, furan,thiophene, and imidazole; and the carbocyclyl is selected from the groupconsisting of cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is -carbocyclyl(R²²)_(j); j is 0; R⁵ is-heterocyclyl(R⁹)_(h); h is 1 or 2; R⁹ is selected from the groupconsisting of halide and —(C₁₋₂ alkyl); and the carbocyclyl is selectedfrom the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is selected from the group consisting of —NR¹⁵R¹⁶ and—CH₂NR¹⁷R¹⁸; R¹⁵ and R¹⁷ are independently selected from the groupconsisting of H and —(C₁₋₃ alkyl); R¹⁶ and R¹⁸ are independentlyselected from the group consisting of H, —(C₁₋₃ alkyl),—CH₂phenyl(R²¹)_(k), and —CH₂carbocyclyl(R²²)_(j), wherein k and j are0; R⁵ is -phenyl(R¹⁰)_(k), wherein k is 1 or 2; R¹⁰ is F; and thecarbocyclyl is selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is selected from the group consisting of —NR¹⁵R¹⁶ and—CH₂NR¹⁷R¹⁸; R¹⁵ and R¹⁷ are independently selected from the groupconsisting of H and —(C₁₋₃ alkyl); R¹⁶ and R¹⁸ are independentlyselected from the group consisting of H, —(C₁₋₃ alkyl),—CH₂phenyl(R²¹)_(k), and —CH₂carbocyclyl(R²²)_(j), wherein k and j are0; R⁵ is -phenyl(R¹⁰)_(k), wherein k is 2; one R¹⁰ is F and the otherR¹⁰ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁹; p is 1; R¹⁹ is —(C₁₋₃ alkyl); andthe carbocyclyl is selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is selected from the group consisting of —NR¹⁵R¹⁶ and—CH₂NR¹⁷R¹⁸, wherein R¹⁵ and R¹⁷ are independently selected from thegroup consisting of H and —(C₁₋₃ alkyl), and R¹⁶ and R¹⁸ areindependently selected from the group consisting of H, —(C₁₋₃ alkyl),—CH₂phenyl(R²¹)_(k), and —CH₂carbocyclyl(R²²)_(j), wherein k and j are0; R⁵ is -phenyl(R¹⁰)_(k), wherein k is 2; one R¹⁰ is F and the otherR¹⁰ is —NH(C₁₋₆ alkylene)NR¹⁵R¹⁶, wherein R¹⁵ and R¹⁶ are independentlyselected from —(C₁₋₃ alkyl); and the carbocyclyl is selected from thegroup consisting of cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q),wherein q is 1; R⁶ is selected from the group consisting of —NR¹⁵R¹⁶ and—CH₂NR¹⁷R¹⁸; R¹⁵ and R¹⁷ are independently selected from the groupconsisting of H and —(C₁₋₃ alkyl); R¹⁶ and R¹⁸ are independentlyselected from the group consisting of H, —(C₁₋₃ alkyl),—CH₂phenyl(R²¹)_(k), and —CH₂carbocyclyl(R²²)_(j); k and j are 0; R⁵ is-heteroaryl(R⁸)_(q), wherein q is 1; R⁸ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁹; R¹⁹ is —(C₁₋₃alkyl); the heteroaryl is selected from the group consisting ofpyridine, furan, thiophene, and imidazole; and the carbocyclyl isselected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, and cyclohexyl.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is selected from the group consisting of —NR¹⁵R¹⁶ and—CH₂NR¹⁷R¹⁸; R¹⁵ and R¹⁷ are independently selected from the groupconsisting of H and —(C₁₋₃ alkyl); R¹⁶ and R¹⁸ are independentlyselected from the group consisting of H, —(C₁₋₃ alkyl),—CH₂phenyl(R²¹)_(k), and —CH₂carbocyclyl(R²²)_(j); k and j are 0; R⁵ is-heterocyclyl(R⁹)_(h); h is 1 or 2; each R⁹ is independently selectedfrom the group consisting of halide and —(C₁₋₂ alkyl); and thecarbocyclyl is selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is —CH₂heterocyclyl(R¹¹)_(h); h is 0-2; R¹¹ is F; R⁵ is-phenyl(R¹⁰)_(k); k is 1 or 2; R¹⁰ is F; and the heterocyclyl isselected from the group consisting of pyrrolidine and piperidine.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is —CH₂heterocyclyl(R¹¹)_(h); h is 0-2; R¹¹ is F; R⁵ is-phenyl(R¹⁰)_(k); k is 2; one R¹⁰ is F and the other R¹⁰ is —(C₁₋₂alkylene)_(p)NHSO₂R¹⁹; p is 1; R⁹ is —(C₁₋₃ alkyl); and the heterocyclylis selected from the group consisting of pyrrolidine and piperidine.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is —CH₂heterocyclyl(R¹¹)_(h); h is 0-2; R¹¹ is F; R⁵ is-phenyl(R¹⁰)_(k); k is 2; one R¹⁰ is F and the other R¹⁰ is —NH(C₁₋₆alkylene)NR¹⁵R¹⁶; R¹⁵ and R¹⁶ are independently selected from —(C₁₋₃alkyl); and the heterocyclyl is selected from the group consisting ofpyrrolidine and piperidine.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q),wherein q is 1; R⁶ is —CH₂heterocyclyl(R¹¹)_(h); h is 0-2; R¹¹ is F; R⁵is -heteroaryl(R⁸)_(q), wherein q is 1; R⁸ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁹; R¹⁹ is —(C₁₋₃alkyl); the heteroaryl is selected from the group consisting ofpyridine, furan, thiophene, and imidazole; and the heterocyclyl isselected from the group consisting of pyrrolidine and piperidine.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is —CH₂heterocyclyl(R¹¹)_(h), wherein h is 0-2; R¹¹ is F; R⁵is -heterocyclyl(R⁹)_(h), wherein h is 1 or 2; each R⁹ is independentlyselected from the group consisting of halide and —(C₁₋₂ alkyl); and theheterocyclyl is selected from the group consisting of pyrrolidine andpiperidine.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyrimidinyl(R⁶)_(q); qis 0; R⁵ is -phenyl(R¹⁰)_(k); k is 1 or 2; and R¹⁰ is F.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyrimidinyl(R⁶); q is0; R⁵ is -phenyl(R¹⁰)_(k); k is 2; one R¹⁰ is F and the other R¹⁰ is—(C₁₋₂ alkylene)_(p)NHSO₂R¹⁹; p is 1; and R¹⁹ is —(C₁₋₃ alkyl).

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyrimidinyl(R⁶)_(q); qis 0; R⁵ is -phenyl(R¹⁰)_(k); k is 2; one R¹⁰ is F and the other R¹⁰ is—NH(C₁₋₆ alkylene)NR¹⁵R¹⁶; and R¹⁵ and R¹⁶ are independently a —(C₁₋₃alkyl).

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyrimidinyl(R⁶)_(q),wherein q is 0; R⁵ is -heteroaryl(R⁸)_(q), wherein q is 1; R⁸ isselected from the group consisting of halide, —(C₁₋₂ alkyl), and—C(═O)R¹⁹; R¹⁹ is —(C₁₋₃ alkyl); and the heteroaryl is selected from thegroup consisting of pyridine, furan, thiophene, and imidazole.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyrimidinyl(R⁶)_(q); qis 0; R⁵ is -heterocyclyl(R⁹)_(h); h is 1 or 2; each R⁹ is independentlyselected from the group consisting of halide and —(C₁₋₂ alkyl).

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is —(C₂₋₅ alkyl);R⁵ is -phenyl(R¹⁰)_(k); k is 1 or 2; and R¹⁰ is F.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is —(C₂₋₅ alkyl);R⁵ is -phenyl(R¹⁰)_(k); k is 2; one R¹⁰ is F and the other R¹⁰ is —(C₁₋₂alkylene)_(p)NHSO₂R¹⁹; p is 1; and R¹⁹ is —(C₁₋₃ alkyl).

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is —(C₂₋₅ alkyl);R⁵ is -phenyl(R¹⁰)_(k); k is 2; one R¹⁰ is F and the other R¹⁰ is—NH(C₁₋₆ alkylene)NR¹⁵R¹⁶; and R¹⁵ and R¹⁶ are independently a —(C₁₋₃alkyl).

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q), wherein q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is —(C₂₋₅alkyl); R⁸ is -heteroaryl(R⁸)_(q), wherein q is 1; R⁸ is selected fromthe group consisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁹; R¹⁹ is—(C₁₋₃ alkyl); and the heteroaryl is selected from the group consistingof pyridine, furan, thiophene, and imidazole.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is —(C₂₋₅ alkyl);R⁵ is -heterocyclyl(R⁹)_(h); h is 1 or 2; and each R⁹ is independentlyselected from the group consisting of halide and —(C₁₋₂ alkyl).

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is-carbocyclyl(R²²); j is 0; R⁵ is -phenyl(R¹⁰)_(k); k is 1 or 2; R¹⁰ isF; and the carbocyclyl is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is-carbocyclyl(R²²); j is 0; R⁵ is -phenyl(R¹⁰)_(k); k is 2; one R¹⁰ is Fand the other R¹⁰ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁹; p is 1; R¹⁹ is —(C₁₋₃alkyl); and the carbocyclyl is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is-carbocyclyl(R²²); j is 0; R⁵ is -phenyl(R¹⁰)_(k); k is 2; one R¹⁰ is Fand the other R¹⁰ is —NH(C₁₋₆ alkylene)NR¹⁵R¹⁶; R¹⁵ and R¹⁶ areindependently a —(C₁₋₃ alkyl); and the carbocyclyl is selected from thegroup consisting of cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q), wherein q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is-carbocyclyl(R²²); j is 0; R⁵ is -heteroaryl(R⁸)_(q), wherein q is 1; R⁸is selected from the group consisting of halide, —(C₁₋₂ alkyl), and—C(═O)R¹⁹; R¹⁹ is —(C₁₋₃ alkyl); the heteroaryl is selected from thegroup consisting of pyridine, furan, thiophene, and imidazole; and thecarbocyclyl is selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is —NHC(═O)R¹⁴; R¹⁴ is-carbocyclyl(R¹²); j is 0; R⁵ is -heterocyclyl(R⁹)_(h); h is 1 or 2;each R⁹ is independently selected from the group consisting of halideand —(C₁₋₂ alkyl); and the carbocyclyl is selected from the groupconsisting of cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is selected from the group consistingof —NR¹⁵R¹⁶ and —CH₂NR¹⁷R¹⁸; R¹⁵ and R¹⁷ are independently selected fromthe group consisting of H and —(C₁₋₃ alkyl); R¹⁶ and R¹⁸ areindependently selected from the group consisting of H, —(C₁₋₃ alkyl),—CH₂phenyl(R²¹)_(k), and —CH₂carbocyclyl(R²²)_(j), wherein k and j are0; R⁵ is -phenyl(R¹⁰)_(k), wherein k is 1 or 2; R¹⁰ is F; and thecarbocyclyl is selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is selected from the group consistingof —NR¹⁵R¹⁶ and —CH₂NR¹⁷R¹⁸; R¹⁵ and R¹⁷ are independently selected fromthe group consisting of H and —(C₁₋₃ alkyl); R¹⁶ and R¹⁸ areindependently selected from the group consisting of H, —(C₁₋₃ alkyl),—CH₂phenyl(R²¹)_(k), and —CH₂carbocyclyl(R²²)_(j), wherein k and j are0; R⁵ is -phenyl(R¹⁰)_(k), wherein k is 2; one R¹⁰ is F and the otherR¹⁰ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁹; p is 1; R¹⁹ is —(C₁₋₃ alkyl); andthe carbocyclyl is selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is selected from the group consistingof —NR¹⁵R¹⁶ and —CH₂NR¹⁷R¹⁸, wherein R¹⁵ and R¹⁷ are independentlyselected from the group consisting of H and —(C₁₋₃ alkyl), and R¹⁶ andR¹⁸ are independently selected from the group consisting of H, —(C₁₋₃alkyl), —CH₂phenyl(R²¹)_(k), and —CH₂carbocyclyl(R²²)_(j), wherein k andj are 0; R⁵ is -phenyl(R¹⁰)_(k), wherein k is 2; one R¹⁰ is F and theother R¹⁰ is —NH(C₁₋₆ alkylene)NR¹⁵R¹⁶, wherein R¹⁵ and R¹⁶ areindependently selected from —(C₁₋₃ alkyl); and the carbocyclyl isselected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q), wherein q is 1; R⁶ is selected from the groupconsisting of —NR¹⁵R¹⁶ and —CH₂NR¹⁷R¹⁸; R¹⁵ and R¹⁷ are independentlyselected from the group consisting of H and —(C₁₋₃ alkyl); R¹⁶ and R¹⁸are independently selected from the group consisting of H, —(C₁₋₃alkyl), —CH₂phenyl(R²¹)_(k), and —CH₂carbocyclyl(R²²)_(j); k and j are0; R⁵ is -heteroaryl(R⁸)_(q), wherein q is 1; R⁸ is selected from thegroup consisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁹; R¹⁹ is —(C₁₋₃alkyl); the heteroaryl is selected from the group consisting ofpyridine, furan, thiophene, and imidazole; and the carbocyclyl isselected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is selected from the group consistingof —NR¹⁵R¹⁶ and —CH₂NR¹⁷R¹⁸; R¹⁵ and R¹⁷ are independently selected fromthe group consisting of H and —(C₁₋₃ alkyl); R¹⁶ and R¹⁸ areindependently selected from the group consisting of H, —(C₁₋₃ alkyl),—CH₂phenyl(R²¹)_(k), and —CH₂carbocyclyl(R²²)_(j); k and j are 0; R⁵ is-heterocyclyl(R⁹)_(h); h is 1 or 2; each R⁹ is independently selectedfrom the group consisting of halide and C₁₋₂ alkyl; and the carbocyclylis selected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is —CH₂heterocyclyl(R¹¹)_(h); h is0-2; R¹¹ is F; R⁵ is -phenyl(R¹⁰)_(k); k is 1 or 2; R¹⁰ is F; and theheterocyclyl is selected from the group consisting of pyrrolidine andpiperidine.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is —CH₂heterocyclyl(R¹¹)_(h); h is0-2; R¹¹ is F; R⁵ is -phenyl(R¹⁰)_(k); k is 2; one R¹⁰ is F and theother R¹⁰ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁹; p is 1; R¹⁹ is —(C₁₋₃ alkyl);and the heterocyclyl is selected from the group consisting ofpyrrolidine and piperidine.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is —CH₂heterocyclyl(R¹¹)_(h); h is0-2; R¹¹ is F; R⁵ is -phenyl(R¹⁰)_(k); k is 2; one R¹⁰ is F and theother R¹⁰ is —NH(C₁₋₆ alkylene)NR¹⁵R¹⁶; R¹⁵ and R¹⁶ are independentlyselected from —(C₁₋₃ alkyl); and the heterocyclyl is selected from thegroup consisting of pyrrolidine and piperidine.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q), wherein q is 1; R⁶ is —CH₂heterocyclyl(R¹¹)_(h);h is 0-2; R¹¹ is F; R⁵ is -heteroaryl(R⁸)_(q), wherein q is 1; R⁸ isselected from the group consisting of halide, —(C₁₋₂ alkyl), and—C(═O)R¹⁹; R¹⁹ is —(C₁₋₃ alkyl); the heteroaryl is selected from thegroup consisting of pyridine, furan, thiophene, and imidazole; and theheterocyclyl is selected from the group consisting of pyrrolidine andpiperidine.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyridin-3-yl(R⁶)_(q); q is 1; R⁶ is —CH₂heterocyclyl(R¹¹)_(h), whereinh is 0-2; R¹¹ is F; R⁵ is -heterocyclyl(R⁹)_(h), wherein h is 1 or 2; R⁹is selected from the group consisting of halide and —(C₁₋₂ alkyl); andthe heterocyclyl is selected from the group consisting of pyrrolidineand piperidine.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyrimidinyl(R⁶)_(q); q is 0; R⁵ is -phenyl(R¹⁰)_(k); k is 1 or 2; andR¹⁰ is F.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyrimidinyl(R⁶)_(q); q is 0; R⁵ is -phenyl(R¹⁰)_(k); k is 2; one R¹⁰ isF and the other R¹⁰ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁹; p is 1; and R¹⁹ is—(C₁₋₃ alkyl).

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyrimidinyl(R⁶)_(q); q is 0; R⁵ is -phenyl(R¹⁰)_(k); k is 2; one R¹⁰ isF and the other R¹⁰ is —NH(C₁₋₆ alkylene)NR¹⁵R¹⁶; and R¹⁵ and R¹⁶ areindependently selected from —(C₁₋₃ alkyl).

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyrimidinyl(R⁶)_(q), wherein q is 0; R⁵ is -heteroaryl(R⁸)_(q); q is 1;R⁸ is selected from the group consisting of halide, —(C₁₋₂ alkyl), and—C(═O)R¹⁹; R¹⁹ is —(C₁₋₃ alkyl); and the heteroaryl is selected from thegroup consisting of pyridine, furan, thiophene, and imidazole.

In some embodiments, R² is F; R¹ and R⁴ are H; R³ is-pyrimidinyl(R⁶)_(q); q is 0; R⁵ is -heterocyclyl(R⁹)_(h); h is 1 or 2;R⁹ is selected from the group consisting of halide and —(C₁₋₂ alkyl).

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyrazol-4-yl(R⁶)_(q);q is 0 or 1; R⁶ is —(C₁₋₃ alkyl); R⁵ is -phenyl(R¹⁰)_(k); k is 1 or 2;and R¹⁰ is F.

In some embodiments, R¹, R², and R⁴ are H; R³ is -imidazol-5-yl(R⁶)_(q);q is 1 or 2; each R⁶ is independently selected from —(C₁₋₃ alkyl); R⁵ is-phenyl(R¹⁰)_(k); k is 1 or 2; and R¹⁰ is F.

In some embodiments, R¹, R², and R⁴ are H; R³ is -pyridin-3-yl(R⁶)_(q);q is 1; R⁶ is —OR²⁴; R²⁴ is selected from the group consisting of H and—(C₁₋₃ alkyl); R⁵ is -phenyl(R¹⁰)_(k); k is 1 or 2; and R¹⁰ is F.

Illustrative compounds of Formula (I) are shown in Table 1.

TABLE 1 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

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1003

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1009

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1011

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1016

1017

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1020

1021

1022

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1024

1025

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1038

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1102

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1104

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1111

1112

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1115

1116

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1118

1119

1120

1121

1122

1123

1124

1125

1126

1127

1128

1129

1130

1131

1132

1133

1134

1135

1136

1137

1138

1139

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Administration and Pharmaceutical Compositions

Some embodiments include pharmaceutical compositions comprising: (a) atherapeutically effective amount of a compound provided herein, or itscorresponding enantiomer, diastereoisomer or tautomer, orpharmaceutically acceptable salt; and (b) a pharmaceutically acceptablecarrier.

The compounds provided herein may also be useful in combination(administered together or sequentially) with other known agents.

Non-limiting examples of diseases which can be treated with acombination of a compound of Formula (I) and other known agents arecolorectal cancer, ovarian cancer, retinitis pigmentosa, maculardegeneration, diabetic retinopathy, idiopathic pulmonaryfibrosis/pulmonary fibrosis, and osteoarthritis.

In some embodiments, colorectal cancer can be treated with a combinationof a compound of Formula (I) and one or more of the following drugs:5-Fluorouracil (5-FU), which can be administered with the vitamin-likedrug leucovorin (also called folinic acid); capecitabine (XELODA®),irinotecan (CAMPOSTAR®), oxaliplatin (ELOXATIN®). Examples ofcombinations of these drugs which could be further combined with acompound of Formula (I) are FOLFOX (5-FU, leucovorin, and oxaliplatin),FOLFIRI (5-FU, leucovorin, and irinotecan), FOLFOXIRI (leucovorin, 5-FU,oxaliplatin, and irinotecan) and CapeOx (Capecitabine and oxaliplatin).For rectal cancer, chemo with 5-FU or capecitabine combined withradiation may be given before surgery (neoadjuvant treatment).

In some embodiments, ovarian cancer can be treated with a combination ofa compound of Formula (I) and one or more of the following drugs:Topotecan, Liposomal doxorubicin (DOXIL®), Gemcitabine (GEMZAR®),Cyclophosphamide (CYTOXAN®), Vinorelbine (NAVELBINE®), Ifosfamide(IFEX®), Etoposide (VP-16), Altretamine (HEXALEN®), Capecitabine(XELODA®), Irinotecan (CPT-11, CAMPTOSAR®), Melphalan, Pemetrexed(ALIMTA®) and Albumin bound paclitaxel (nab-paclitaxel, ABRAXANE®).Examples of combinations of these drugs which could be further combinedwith a compound of Formula (I) are TIP (paclitaxel [Taxol], ifosfamide,and cisplatin), VeIP (vinblastine, ifosfamide, and cisplatin) and VIP(etoposide [VP-16], ifosfamide, and cisplatin).

In some embodiments, a compound of Formula (I) can be used to treatcancer in combination with any of the following methods: (a) Hormonetherapy such as aromatase inhibitors, LHRH [luteinizinghormone-releasing hormone] analogs and inhibitors, and others; (b)Ablation or embolization procedures such as radiofrequency ablation(RFA), ethanol (alcohol) ablation, microwave thermotherapy andcryosurgery (cryotherapy); (c) Chemotherapy using alkylating agents suchas cisplatin and carboplatin, oxaliplatin, mechlorethamine,cyclophosphamide, chlorambucil and ifosfamide; (d) Chemotherapy usinganti-metabolites such as azathioprine and mercaptopurine; (e)Chemotherapy using plant alkaloids and terpenoids such as vincaalkaloids (i.e. Vincristine, Vinblastine, Vinorelbine and Vindesine) andtaxanes; (f) Chemotherapy using podophyllotoxin, etoposide, teniposideand docetaxel; (g) Chemotherapy using topoisomerase inhibitors such asirinotecan, topotecan, amsacrine, etoposide, etoposide phosphate, andteniposide; (h) Chemotherapy using cytotoxic antibiotics such asactinomycin, anthracyclines, doxorubicin, daunorubicin, valrubicin,idarubicin, epirubicin, bleomycin, plicamycin and mitomycin; (i)Chemotherapy using tyrosine-kinase inhibitors such as Imatinib mesylate(GLEEVEC®, also known as STI-571), Gefitinib (Iressa, also known asZD1839), Erlotinib (marketed as TARCEVA®), Bortezomib (VELCADE®),tamoxifen, tofacitinib, crizotinib, Bcl-2 inhibitors (e.g. obatoclax inclinical trials, ABT-263, and Gossypol), PARP inhibitors (e.g. Iniparib,Olaparib in clinical trials), PI3K inhibitors (eg. perifosine in a phaseIII trial), VEGF Receptor 2 inhibitors (e.g. Apatinib), AN-152,(AEZS-108), Braf inhibitors (e.g. vemurafenib, dabrafenib and LGX818),MEK inhibitors (e.g. trametinib and MEK162), CDK inhibitors, (e.g.PD-0332991), salinomycin and Sorafenib; (j) Chemotherapy usingmonoclonal antibodies such as Rituximab (marketed as MABTHERA® orRITUXAN®), Trastuzumab (Herceptin also known as ErbB2), Cetuximab(marketed as ERBITUX®), and Bevacizumab (marketed as AVASTIN®); and (k)radiation therapy.

In some embodiments, diabetic retinopathy can be treated with acombination of a compound of Formula (I) and one or more of thefollowing natural supplements: Bilberry, Butcher's broom, Ginkgo, Grapeseed extract, and Pycnogenol (Pine bark).

In some embodiments, idiopathic pulmonary fibrosis/pulmonary fibrosiscan be treated with a combination of a compound of Formula (I) and oneor more of the following drugs: pirfenidone (pirfenidone was approvedfor use in 2011 in Europe under the brand name Esbriet®), prednisone,azathioprine, N-acetylcysteine, interferon-γ lb, bosentan (bosentan iscurrently being studied in patients with IPF, [The American JournalofRespiratory and Critical Care Medicine (2011), 184(1), 92-9]),Nintedanib (BIBF 1120 and Vargatef), QAX576 [British Journal ofPharmacology (2011), 163(1), 141-172], and anti-inflammatory agents suchas corticosteroids.

In some embodiments, a compound of Formula (I) can be used to treatidiopathic pulmonary fibrosis/pulmonary fibrosis in combination with anyof the following methods: oxygen therapy, pulmonary rehabilitation andsurgery.

In some embodiments, a compound of Formula (I) can be used to treatosteoarthritis in combination with any of the following methods: (a)Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen,naproxen, aspirin and acetaminophen; (b) physical therapy; (c)injections of corticosteroid medications; (d) injections of hyaluronicacid derivatives (e.g. Hyalgan, Synvisc); (e) narcotics, like codeine;(f) in combination with braces and/or shoe inserts or any device thatcan immobilize or support your joint to help you keep pressure off it(e.g., splints, braces, shoe inserts or other medical devices); (g)realigning bones (osteotomy); (h) joint replacement (arthroplasty); and(i) in combination with a chronic pain class.

In some embodiments, macular degeneration can be treated with acombination of a compound of Formula (I) and one or more of thefollowing drugs: Bevacizumab (Avastin®), Ranibizumab (Lucentis®),Pegaptanib (Macugen), Aflibercept (Eylea®), verteporfin (Visudyne®) incombination with photodynamic therapy (PDT) or with any of the followingmethods: (a) in combination with laser to destroy abnormal blood vessels(photocoagulation); and (b) in combination with increased vitamin intakeof antioxidant vitamins and zinc.

In some embodiments, retinitis pigmentosa can be treated with acombination of a compound of Formula (I) and one or more of thefollowing drugs: UF-021 (Ocuseva™), vitamin A palmitate and pikachurinor with any of the following methods: (a) with the Argus® II retinalimplant; and (b) with stem cell and/or gene therapy.

Administration of the compounds disclosed herein or the pharmaceuticallyacceptable salts thereof can be via any of the accepted modes ofadministration, including, but not limited to, orally, subcutaneously,intravenously, intranasally, topically, transdermally,intraperitoneally, intramuscularly, intrapulmonarilly, vaginally,rectally, ontologically, neuro-otologically, intraocularly,subconjuctivally, via anterior eye chamber injection, intravitreally,intraperitoneally, intrathecally, intracystically, intrapleurally, viawound irrigation, intrabuccally, intra-abdominally, intra-articularly,intra-aurally, intrabronchially, intracapsularly, intrameningeally, viainhalation, via endotracheal or endobronchial instillation, via directinstillation into pulmonary cavities, intraspinally, intrasynovially,intrathoracically, via thoracostomy irrigation, epidurally,intratympanically, intracisternally, intravascularly,intraventricularly, intraosseously, via irrigation of infected bone, orvia application as part of any admixture with a prosthetic devices. Insome embodiments, the administration method includes oral or parenteraladministration.

Compounds provided herein intended for pharmaceutical use may beadministered as crystalline or amorphous products. Pharmaceuticallyacceptable compositions may include solid, semi-solid, liquid,solutions, colloidal, liposomes, emulsions, suspensions, complexes,coacervates and aerosols. Dosage forms, such as, e.g., tablets,capsules, powders, liquids, suspensions, suppositories, aerosols,implants, controlled release or the like. They may be obtained, forexample, as solid plugs, powders, or films by methods such asprecipitation, crystallization, milling, grinding, supercritical fluidprocessing, coacervation, complex coacervation, encapsulation,emulsification, complexation, freeze drying, spray drying, orevaporative drying. Microwave or radio frequency drying may be used forthis purpose. The compounds can also be administered in sustained orcontrolled release dosage forms, including depot injections, osmoticpumps, pills (tablets and or capsules), transdermal (includingelectrotransport) patches, implants and the like, for prolonged and/ortimed, pulsed administration at a predetermined rate.

The compounds can be administered either alone or in combination with aconventional pharmaceutical carrier, excipient or the like.Pharmaceutically acceptable excipients include, but are not limited to,ion exchangers, alumina, aluminum stearate, lecithin, self-emulsifyingdrug delivery systems (SEDDS) such as d-α-tocopherol polyethylene glycol1000 succinate, surfactants used in pharmaceutical dosage forms such asTweens, poloxamers or other similar polymeric delivery matrices, serumproteins, such as human serum albumin, buffer substances such asphosphates, tris, glycine, sorbic acid, potassium sorbate, partialglyceride mixtures of saturated vegetable fatty acids, water, salts orelectrolytes, such as protamine sulfate, disodium hydrogen phosphate,potassium hydrogen phosphate, sodium-chloride, zinc salts, colloidalsilica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-basedsubstances, polyethylene glycol, sodium carboxymethyl cellulose,polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, andwool fat. Cyclodextrins such as α-, β, and γ-cyclodextrin, or chemicallymodified derivatives such as hydroxyalkylcyclodextrins, including 2- and3-hydroxypropyl-β-cyclodextrins, or other solubilized derivatives canalso be used to enhance delivery of compounds described herein. Dosageforms or compositions containing a compound as described herein in therange of 0.005% to 100% with the balance made up from non-toxic carriermay be prepared. The contemplated compositions may contain 0.001%-100%of a compound provided herein, in one embodiment 0.1-95%, in anotherembodiment 75-85%, in a further embodiment 20-80%. Actual methods ofpreparing such dosage forms are known, or will be apparent, to thoseskilled in this art; for example, see Remington: The Science andPractice of Pharmacy, 22^(nd) Edition (Pharmaceutical Press, London, UK.2012).

In one embodiment, the compositions will take the form of a unit dosageform such as a pill or tablet and thus the composition may contain,along with a compound provided herein, a diluent such as lactose,sucrose, dicalcium phosphate, or the like; a lubricant such as magnesiumstearate or the like; and a binder such as starch, gum acacia,polyvinylpyrrolidine, gelatin, cellulose, cellulose derivatives or thelike. In another solid dosage form, a powder, marume, solution orsuspension (e.g., in propylene carbonate, vegetable oils, PEG's,poloxamer 124 or triglycerides) is encapsulated in a capsule (gelatin orcellulose base capsule). Unit dosage forms in which one or morecompounds provided herein or additional active agents are physicallyseparated are also contemplated; e.g., capsules with granules (ortablets in a capsule) of each drug; two-layer tablets; two-compartmentgel caps, etc. Enteric coated or delayed release oral dosage forms arealso contemplated.

Liquid pharmaceutically administrable compositions can, for example, beprepared by dissolving, dispersing, etc. a compound provided herein andoptional pharmaceutical adjuvants in a carrier (e.g., water, saline,aqueous dextrose, glycerol, glycols, ethanol or the like) to form asolution, colloid, liposome, emulsion, complexes, coacervate orsuspension. If desired, the pharmaceutical composition can also containminor amounts of nontoxic auxiliary substances such as wetting agents,emulsifying agents, co-solvents, solubilizing agents, pH bufferingagents and the like (e.g., sodium acetate, sodium citrate, cyclodextrinderivatives, sorbitan monolaurate, triethanolamine acetate,triethanolamine oleate, and the like).

In some embodiments, the unit dosage of compounds of Formula (I) isabout 0.25 mg/Kg to about 50 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 0.25 mg/Kg to about 20 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 0.50 mg/Kg to about 19 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 0.75 mg/Kg to about 18 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 1.0 mg/Kg to about 17 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 1.25 mg/Kg to about 16 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 1.50 mg/Kg to about 15 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 1.75 mg/Kg to about 14 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 2.0 mg/Kg to about 13 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 3.0 mg/Kg to about 12 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 4.0 mg/Kg to about 11 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 5.0 mg/Kg to about 10 mg/Kg in humans.

In some embodiments, the compositions are provided in unit dosage formssuitable for single administration.

In some embodiments, the compositions are provided in unit dosage formssuitable for twice a day administration.

In some embodiments, the compositions are provided in unit dosage formssuitable for three times a day administration.

Injectables can be prepared in conventional forms, either as liquidsolutions, colloid, liposomes, complexes, coacervate or suspensions, asemulsions, or in solid forms suitable for reconstitution in liquid priorto injection. The percentage of a compound provided herein contained insuch parenteral compositions is highly dependent on the specific naturethereof, as well as the activity of the compound and the needs of thepatient. However, percentages of active ingredient of 0.01% to 10% insolution are employable, and could be higher if the composition is asolid or suspension, which could be subsequently diluted to the abovepercentages.

In some embodiments, the composition will comprise about 0.1-10% of theactive agent in solution.

In some embodiments, the composition will comprise about 0.1-5% of theactive agent in solution.

In some embodiments, the composition will comprise about 0.1-4% of theactive agent in solution.

In some embodiments, the composition will comprise about 0.15-3% of theactive agent in solution.

In some embodiments, the composition will comprise about 0.2-2% of theactive agent in solution.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-96 hours.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-72 hours.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-48 hours.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-24 hours.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-12 hours.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-6 hours.

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 5 mg/m² to about 300mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 5 mg/m² to about 200mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 5 mg/m² to about 100mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 10 mg/m² to about 50mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 50 mg/m² to about 200mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 75 mg/m² to about 175mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 100 mg/m² to about 150mg/m².

It is to be noted that concentrations and dosage values may also varydepending on the specific compound and the severity of the condition tobe alleviated. It is to be further understood that for any particularpatient, specific dosage regimens should be adjusted over time accordingto the individual need and the professional judgment of the personadministering or supervising the administration of the compositions, andthat the concentration ranges set forth herein are exemplary only andare not intended to limit the scope or practice of the claimedcompositions.

In one embodiment, the compositions can be administered to therespiratory tract (including nasal and pulmonary) e.g., through anebulizer, metered-dose inhalers, atomizer, mister, aerosol, dry powderinhaler, insufflator, liquid instillation or other suitable device ortechnique.

In some embodiments, aerosols intended for delivery to the nasal mucosaare provided for inhalation through the nose. For optimal delivery tothe nasal cavities, inhaled particle sizes of about 5 to about 100microns are useful, with particle sizes of about 10 to about 60 micronsbeing preferred. For nasal delivery, a larger inhaled particle size maybe desired to maximize impaction on the nasal mucosa and to minimize orprevent pulmonary deposition of the administered formulation. In someembodiments, aerosols intended for delivery to the lung are provided forinhalation through the nose or the mouth. For delivery to the lung,inhaled aerodynamic particle sizes of about less than 10 μm are useful(e.g., about 1 to about 10 microns). Inhaled particles may be defined asliquid droplets containing dissolved drug, liquid droplets containingsuspended drug particles (in cases where the drug is insoluble in thesuspending medium), dry particles of pure drug substance, drug substanceincorporated with excipients, liposomes, emulsions, colloidal systems,coacervates, aggregates of drug nanoparticles, or dry particles of adiluent which contain embedded drug nanoparticles.

In some embodiments, compounds of Formula (I) disclosed herein intendedfor respiratory delivery (either systemic or local) can be administeredas aqueous formulations, as non-aqueous solutions or suspensions, assuspensions or solutions in halogenated hydrocarbon propellants with orwithout alcohol, as a colloidal system, as emulsions, coacervates, or asdry powders. Aqueous formulations may be aerosolized by liquidnebulizers employing either hydraulic or ultrasonic atomization or bymodified micropump systems (like the soft mist inhalers, the Aerodose®or the AERx® systems). Propellant-based systems may use suitablepressurized metered-dose inhalers (pMDIs). Dry powders may use drypowder inhaler devices (DPIs), which are capable of dispersing the drugsubstance effectively. A desired particle size and distribution may beobtained by choosing an appropriate device.

In some embodiments, the compositions of Formula (I) disclosed hereincan be administered to the ear by various methods. For example, a roundwindow catheter (e.g., U.S. Pat. Nos. 6,440,102 and 6,648,873) can beused.

Alternatively, formulations can be incorporated into a wick for usebetween the outer and middle ear (e.g., U.S. Pat. No. 6,120,484) orabsorbed to collagen sponge or other solid support (e.g., U.S. Pat. No.4,164,559).

If desired, formulations of the invention can be incorporated into a gelformulation (e.g., U.S. Pat. Nos. 4,474,752 and 6,911,211).

In some embodiments, compounds of Formula (I) disclosed herein intendedfor delivery to the ear can be administered via an implanted pump anddelivery system through a needle directly into the middle or inner ear(cochlea) or through a cochlear implant stylet electrode channel oralternative prepared drug delivery channel such as but not limited to aneedle through temporal bone into the cochlea.

Other options include delivery via a pump through a thin film coatedonto a multichannel electrode or electrode with a specially imbeddeddrug delivery channel (pathways) carved into the thin film for thispurpose. In other embodiments the acidic or basic solid compound ofFormula (I) can be delivered from the reservoir of an external orinternal implanted pumping system.

Formulations of the invention also can be administered to the ear byintratympanic injection into the middle ear, inner ear, or cochlea(e.g., U.S. Pat. No. 6,377,849 and Ser. No. 11/337,815).

Intratympanic injection of therapeutic agents is the technique ofinjecting a therapeutic agent behind the tympanic membrane into themiddle and/or inner ear. In one embodiment, the formulations describedherein are administered directly onto the round window membrane viatranstympanic injection. In another embodiment, the ion channelmodulating agent auris-acceptable formulations described herein areadministered onto the round window membrane via a non-transtympanicapproach to the inner ear. In additional embodiments, the formulationdescribed herein is administered onto the round window membrane via asurgical approach to the round window membrane comprising modificationof the crista fenestrae cochleae.

In some embodiments, the compounds of Formula (I) are formulated inrectal compositions such as enemas, rectal gels, rectal foams, rectalaerosols, suppositories, jelly suppositories, or retention enemas,containing conventional suppository bases such as cocoa butter or otherglycerides, as well as synthetic polymers such as polyvinylpyrrolidone,PEG (like PEG ointments), and the like.

Suppositories for rectal administration of the drug (either as asolution, colloid, suspension or a complex) can be prepared by mixing acompound provided herein with a suitable non-irritating excipient thatis solid at ordinary temperatures but liquid at the rectal temperatureand will therefore melt or erode/dissolve in the rectum and release thecompound. Such materials include cocoa butter, glycerinated gelatin,hydrogenated vegetable oils, poloxamers, mixtures of polyethyleneglycols of various molecular weights and fatty acid esters ofpolyethylene glycol. In suppository forms of the compositions, alow-melting wax such as, but not limited to, a mixture of fatty acidglycerides, optionally in combination with cocoa butter, is firstmelted.

Solid compositions can be provided in various different types of dosageforms, depending on the physicochemical properties of the compoundprovided herein, the desired dissolution rate, cost considerations, andother criteria. In one of the embodiments, the solid composition is asingle unit. This implies that one unit dose of the compound iscomprised in a single, physically shaped solid form or article. In otherwords, the solid composition is coherent, which is in contrast to amultiple unit dosage form, in which the units are incoherent.

Examples of single units which may be used as dosage forms for the solidcomposition include tablets, such as compressed tablets, film-likeunits, foil-like units, wafers, lyophilized matrix units, and the like.In one embodiment, the solid composition is a highly porous lyophilizedform. Such lyophilizates, sometimes also called wafers or lyophilizedtablets, are particularly useful for their rapid disintegration, whichalso enables the rapid dissolution of the compound.

On the other hand, for some applications the solid composition may alsobe formed as a multiple unit dosage form as defined above. Examples ofmultiple units are powders, granules, microparticles, pellets,mini-tablets, beads, lyophilized powders, and the like. In oneembodiment, the solid composition is a lyophilized powder. Such adispersed lyophilized system comprises a multitude of powder particles,and due to the lyophilization process used in the formation of thepowder, each particle has an irregular, porous microstructure throughwhich the powder is capable of absorbing water very rapidly, resultingin quick dissolution. Effervescent compositions are also contemplated toaid the quick dispersion and absorption of the compound.

Another type of multiparticulate system which is also capable ofachieving rapid drug dissolution is that of powders, granules, orpellets from water-soluble excipients which are coated with a compoundprovided herein so that the compound is located at the outer surface ofthe individual particles. In this type of system, the water-soluble lowmolecular weight excipient may be useful for preparing the cores of suchcoated particles, which can be subsequently coated with a coatingcomposition comprising the compound and, for example, one or moreadditional excipients, such as a binder, a pore former, a saccharide, asugar alcohol, a film-forming polymer, a plasticizer, or otherexcipients used in pharmaceutical coating compositions.

Also provided herein are kits. Typically, a kit includes one or morecompounds or compositions as described herein. In certain embodiments, akit can include one or more delivery systems, e.g., for delivering oradministering a compound as provided herein, and directions for use ofthe kit (e.g., instructions for treating a patient). In anotherembodiment, the kit can include a compound or composition as describedherein and a label that indicates that the contents are to beadministered to a patient with cancer. In another embodiment, the kitcan include a compound or composition as described herein and a labelthat indicates that the contents are to be administered to a patientwith one or more of hepatocellular carcinoma, colon cancer, leukemia,lymphoma, sarcoma, ovarian cancer, diabetic retinopathy, pulmonaryfibrosis, rheumatoid arthritis, sepsis, anklyosing spondylitis,psoriasis, scleroderma, mycotic and viral infections, bone and cartilagediseases, Alzheimer's disease, lung disease, bone/osteoporotic (wrist,spine, shoulder and hip) fractures, articular cartilage (chondral)defects, degenerative disc disease (or intervertebral discdegeneration), polyposis coli, bone density and vascular defects in theeye (Osteoporosis-pseudoglioma Syndrome, OPPG) and other eye diseases orsyndromes associated with defects and/or damaged photoreceptors,familial exudative vitreoretinopathy, retinal angiogenesis, earlycoronary disease, tetra-amelia, Müllerian-duct regression andvirilization, SERKAL syndrome, type II diabetes, Fuhrmann syndrome,Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome,odonto-onycho-dermal dysplasia, obesity, split-hand/foot malformation,caudal duplication, tooth agenesis, Wilms tumor, skeletal dysplasia,focal dermal hypoplasia, autosomal recessive anonychia, neural tubedefects, alpha-thalassemia (ATRX) syndrome, fragile X syndrome, ICFsyndrome, Angelman's syndrome, Prader-Willi syndrome, Beckwith-WiedemannSyndrome, Norrie disease, and Rett syndrome.

Methods of Treatment

The compounds and compositions provided herein can be used as inhibitorsand/or modulators of one or more components of the Wnt pathway, whichmay include one or more Wnt proteins, and thus can be used to treat avariety of disorders and diseases in which aberrant Wnt signaling isimplicated, such as cancer and other diseases associated with abnormalangiogenesis, cellular proliferation, and cell cycling. Accordingly, thecompounds and compositions provided herein can be used to treat cancer,to reduce or inhibit angiogenesis, to reduce or inhibit cellularproliferation, to correct a genetic disorder, and/or to treat aneurological condition/disorder/disease due to mutations ordysregulation of the Wnt pathway and/or of one or more of Wnt signalingcomponents. Non-limiting examples of diseases which can be treated withthe compounds and compositions provided herein include a variety ofcancers, diabetic retinopathy, pulmonary fibrosis, rheumatoid arthritis,scleroderma, mycotic and viral infections, bone and cartilage diseases,neurological conditions/diseases such as Alzheimer's disease,amyotrophic lateral sclerosis (ALS), motor neuron disease, multiplesclerosis or autism, lung disease, bone/osteoporotic (wrist, spine,shoulder and hip) fractures, polyposis coli, bone density and vasculardefects in the eye (Osteoporosis-pseudoglioma Syndrome, OPPG) and othereye diseases or syndromes associated with defects and/or damagedphotoreceptors, familial exudative vitreoretinopathy, retinalangiogenesis, early coronary disease, tetra-amelia, Müllerian-ductregression and virilization, SERKAL syndrome, type II diabetes, Fuhrmannsyndrome, Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome,odonto-onycho-dermal dysplasia, obesity, split-hand/foot malformation,caudal duplication, tooth agenesis, Wilms tumor, skeletal dysplasia,focal dermal hypoplasia, autosomal recessive anonychia, neural tubedefects, alpha-thalassemia (ATRX) syndrome, fragile X syndrome, ICFsyndrome, Angelman's syndrome, Prader-Willi syndrome, Beckwith-WiedemannSyndrome, Norrie disease and Rett syndrome.

In some embodiments, non-limiting examples of eye diseases which can betreated with the compounds and compositions provided herein includeage-related macular degeneration (AMD or ARMD), rod cone dystrophy,retinitis pigmentosa (RP), acute idiopathic blind spot enlargement(AIBSE), acute zonal occult outer retinopathy (AZOOR), acute macularneuroretinopathy (AMN), multiple evanescent white dot syndrome (MEWDS),multifocal choroiditis, opticneuropathy. Further causes of photoreceptordamage that can be treated with the compounds and compositions providedherein include retinal detachment, vascular disturbance, eye tumors orextreme light damage.

With respect to cancer, the Wnt pathway is known to be constitutivelyactivated in a variety of cancers including, for example, colon cancer,hepatocellular carcinoma, lung cancer, ovarian cancer, prostate cancer,pancreatic cancer and leukemias such as CML, CLL and T-ALL. Accordingly,the compounds and compositions described herein may be used to treatthese cancers in which the Wnt pathway is constitutively activated. Incertain embodiments, the cancer is chosen from hepatocellular carcinoma,colon cancer, leukemia, lymphoma, sarcoma and ovarian cancer.

Other cancers can also be treated with the compounds and compositionsdescribed herein.

More particularly, cancers that may be treated by the compounds,compositions and methods described herein include, but are not limitedto, the following:

1) Breast cancers, including, for example ER⁺ breast cancer, ER⁻ breastcancer, her2⁻ breast cancer, her2⁺ breast cancer, stromal tumors such asfibroadenomas, phyllodes tumors, and sarcomas, and epithelial tumorssuch as large duct papillomas; carcinomas of the breast including insitu (noninvasive) carcinoma that includes ductal carcinoma in situ(including Paget's disease) and lobular carcinoma in situ, and invasive(infiltrating) carcinoma including, but not limited to, invasive ductalcarcinoma, invasive lobular carcinoma, medullary carcinoma, colloid(mucinous) carcinoma, tubular carcinoma, and invasive papillarycarcinoma; and miscellaneous malignant neoplasms. Further examples ofbreast cancers can include luminal A, luminal B, basal A, basal B, andtriple negative breast cancer, which is estrogen receptor negative(ER⁻), progesterone receptor negative, and her2 negative (her2⁻). Insome embodiments, the breast cancer may have a high risk Oncotype score.

2) Cardiac cancers, including, for example sarcoma, e.g., angiosarcoma,fibrosarcoma, rhabdomyosarcoma, and liposarcoma; myxoma; rhabdomyoma;fibroma; lipoma and teratoma.

3) Lung cancers, including, for example, bronchogenic carcinoma, e.g.,squamous cell, undifferentiated small cell, undifferentiated large cell,and adenocarcinoma; alveolar and bronchiolar carcinoma; bronchialadenoma; sarcoma; lymphoma; chondromatous hamartoma; and mesothelioma.

4) Gastrointestinal cancer, including, for example, cancers of theesophagus, e.g., squamous cell carcinoma, adenocarcinoma,leiomyosarcoma, and lymphoma; cancers of the stomach, e.g., carcinoma,lymphoma, and leiomyosarcoma; cancers of the pancreas, e.g., ductaladenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumors,and vipoma; cancers of the small bowel, e.g., adenocarcinoma, lymphoma,carcinoid tumors, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma,neurofibroma, and fibroma; cancers of the large bowel, e.g.,adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, andleiomyoma.

5) Genitourinary tract cancers, including, for example, cancers of thekidney, e.g., adenocarcinoma, Wilm's tumor (nephroblastoma), lymphoma,and leukemia; cancers of the bladder and urethra, e.g., squamous cellcarcinoma, transitional cell carcinoma, and adenocarcinoma; cancers ofthe prostate, e.g., adenocarcinoma, and sarcoma; cancer of the testis,e.g., seminoma, teratoma, embryonal carcinoma, teratocarcinoma,choriocarcinoma, sarcoma, interstitial cell carcinoma, fibroma,fibroadenoma, adenomatoid tumors, and lipoma.

6) Liver cancers, including, for example, hepatoma, e.g., hepatocellularcarcinoma; cholangiocarcinoma; hepatoblastoma; angiosarcoma;hepatocellular adenoma; and hemangioma.

7) Bone cancers, including, for example, osteogenic sarcoma(osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma,chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticulum cellsarcoma), multiple myeloma, malignant giant cell tumor chordoma,osteochrondroma (osteocartilaginous exostoses), benign chondroma,chondroblastoma, chondromyxofibroma, osteoid osteoma and giant celltumors.

8) Nervous system cancers, including, for example, cancers of the skull,e.g., osteoma, hemangioma, granuloma, xanthoma, and osteitis deformans;cancers of the meninges, e.g., meningioma, meningiosarcoma, andgliomatosis; cancers of the brain, e.g., astrocytoma, medulloblastoma,glioma, ependymoma, germinoma (pinealoma), glioblastoma multiform,oligodendroglioma, schwannoma, retinoblastoma, and congenital tumors;and cancers of the spinal cord, e.g., neurofibroma, meningioma, glioma,and sarcoma.

9) Gynecological cancers, including, for example, cancers of the uterus,e.g., endometrial carcinoma; cancers of the cervix, e.g., cervicalcarcinoma, and pre tumor cervical dysplasia; cancers of the ovaries,e.g., ovarian carcinoma, including serous cystadenocarcinoma, mucinouscystadenocarcinoma, unclassified carcinoma, granulosa theca cell tumors,Sertoli Leydig cell tumors, dysgerminoma, and malignant teratoma;cancers of the vulva, e.g., squamous cell carcinoma, intraepithelialcarcinoma, adenocarcinoma, fibrosarcoma, and melanoma; cancers of thevagina, e.g., clear cell carcinoma, squamous cell carcinoma, botryoidsarcoma, and embryonal rhabdomyosarcoma; and cancers of the fallopiantubes, e.g., carcinoma.

10) Hematologic cancers, including, for example, cancers of the blood,e.g., acute myeloid leukemia, chronic myeloid leukemia, acutelymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferativediseases, multiple myeloma, and myelodysplastic syndrome, Hodgkin'slymphoma, non-Hodgkin's lymphoma (malignant lymphoma) and Waldenstrom'smacroglobulinemia.

11) Skin cancers and skin disorders, including, for example, malignantmelanoma and metastatic melanoma, basal cell carcinoma, squamous cellcarcinoma, Kaposi's sarcoma, moles dysplastic nevi, lipoma, angioma,dermatofibroma, keloids, and scleroderma.

12) Adrenal gland cancers, including, for example, neuroblastoma.

Cancers may be solid tumors that may or may not be metastatic. Cancersmay also occur, as in leukemia, as a diffuse tissue. Thus, the term“tumor cell,” as provided herein, includes a cell afflicted by any oneof the above identified disorders.

A method of treating cancer using a compound or composition as describedherein may be combined with existing methods of treating cancers, forexample by chemotherapy, irradiation, or surgery (e.g., oophorectomy).In some embodiments, a compound or composition can be administeredbefore, during, or after another anticancer agent or treatment.

The compounds and compositions described herein can be used asanti-angiogenesis agents and as agents for modulating and/or inhibitingthe activity of protein kinases, thus providing treatments for cancerand other diseases associated with cellular proliferation mediated byprotein kinases. For example, the compounds described herein can inhibitthe activity of one or more kinases. Accordingly, provided herein is amethod of treating cancer or preventing or reducing angiogenesis throughkinase inhibition.

In addition, and including treatment of cancer, the compounds andcompositions described herein can function as cell-cycle control agentsfor treating proliferative disorders in a patient. Disorders associatedwith excessive proliferation include, for example, cancers, scleroderma,immunological disorders involving undesired proliferation of leukocytes,and restenosis and other smooth muscle disorders. Furthermore, suchcompounds may be used to prevent de-differentiation of post-mitotictissue and/or cells.

Diseases or disorders associated with uncontrolled or abnormal cellularproliferation include, but are not limited to, the following:

-   -   a variety of cancers, including, but not limited to, carcinoma,        hematopoietic tumors of lymphoid lineage, hematopoietic tumors        of myeloid lineage, tumors of mesenchymal origin, tumors of the        central and peripheral nervous system and other tumors including        melanoma, seminoma and Kaposi's sarcoma.    -   a disease process which features abnormal cellular        proliferation, e.g., benign prostatic hyperplasia, familial        adenomatosis polyposis, neurofibromatosis, atherosclerosis,        arthritis, glomerulonephritis, restenosis following angioplasty        or vascular surgery, inflammatory bowel disease, transplantation        rejection, endotoxic shock, and fungal infections. Fibrotic        disorders such as skin fibrosis; scleroderma; progressive        systemic fibrosis; lung fibrosis; muscle fibrosis; kidney        fibrosis; glomerulosclerosis; glomerulonephritis; hypertrophic        scar formation; uterine fibrosis; renal fibrosis; cirrhosis of        the liver, liver fibrosis; fatty liver disease (FLD); adhesions,        such as those occurring in the abdomen, pelvis, spine or        tendons; chronic obstructive pulmonary disease; fibrosis        following myocardial infarction; pulmonary fibrosis; fibrosis        and scarring associated with diffuse/interstitial lung disease;        central nervous system fibrosis, such as fibrosis following        stroke; fibrosis associated with neuro-degenerative disorders        such as Alzheimer's Disease or multiple sclerosis; fibrosis        associated with proliferative vitreoretinopathy (PVR);        restenosis; endometriosis; ischemic disease and radiation        fibrosis.    -   defective apoptosis-associated conditions, such as cancers        (including but not limited to those types mentioned herein),        viral infections (including but not limited to herpesvirus,        poxvirus, Epstein-Barr virus, Sindbis virus and adenovirus),        prevention of AIDS development in HIV-infected individuals,        autoimmune diseases (including but not limited to systemic lupus        erythematosus, rheumatoid arthritis, sepsis, anklyosing        spondylitis, psoriasis, scleroderma, autoimmune mediated        glomerulonephritis, inflammatory bowel disease and autoimmune        diabetes mellitus), neuro-degenerative disorders (including but        not limited to Alzheimer's disease, lung disease, amyotrophic        lateral sclerosis, retinitis pigmentosa, Parkinson's disease,        AIDS-related dementia, spinal muscular atrophy and cerebellar        degeneration), myelodysplastic syndromes, aplastic anemia,        ischemic injury associated with myocardial infarctions, stroke        and reperfusion injury, arrhythmia, atherosclerosis,        toxin-induced or alcohol related liver diseases, hematological        diseases (including but not limited to chronic anemia and        aplastic anemia), degenerative diseases of the musculoskeletal        system (including but not limited to osteoporosis and        arthritis), tendinopathies such as tendinitis and tendinosis,        aspirin-sensitive rhinosinusitis, cystic fibrosis, multiple        sclerosis, kidney diseases and cancer pain.    -   genetic diseases due to mutations in Wnt signaling components,        such as polyposis coli, bone density and vascular defects in the        eye (Osteoporosis-pseudoglioma Syndrome, OPPG) and other eye        diseases or syndromes associated with defects and/or damaged        photoreceptors, familial exudative vitreoretinopathy, retinal        angiogenesis, early coronary disease, tetra-amelia,        Müllerian-duct regression and virilization, SERKAL syndrome,        type II diabetes, Fuhrmann syndrome,        Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome,        odonto-onycho-dermal dysplasia, obesity, split-hand/foot        malformation, caudal duplication, tooth agenesis, Wilms tumor,        skeletal dysplasia, focal dermal hypoplasia, autosomal recessive        anonychia, neural tube defects, alpha-thalassemia (ATRX)        syndrome, fragile X syndrome, ICF syndrome, Angelman's syndrome,        Prader-Willi syndrome, Beckwith-Wiedemann Syndrome, Norrie        disease and Rett syndrome.

The compounds and compositions described herein can be used to treatneurological conditions, disorders and/or diseases caused by dysfunctionin the Wnt signaling pathway. Non-limiting examples of neurologicalconditions/disorders/diseases which can be treated with the compoundsand compositions provided herein include Alzheimer's disease, aphasia,apraxia, arachnoiditis, ataxia telangiectasia, attention deficithyperactivity disorder, auditory processing disorder, autism,alcoholism, Bell's palsy, bipolar disorder, brachial plexus injury,Canavan disease, carpal tunnel syndrome, causalgia, central painsyndrome, central pontine myelinolysis, centronuclear myopathy, cephalicdisorder, cerebral aneurysm, cerebral arteriosclerosis, cerebralatrophy, cerebral gigantism, cerebral palsy, cerebral vasculitis,cervical spinal stenosis, Charcot-Marie-Tooth disease, Chiarimalformation, chronic fatigue syndrome, chronic inflammatorydemyelinating polyneuropathy (CIDP), chronic pain, Coffin-Lowrysyndrome, complex regional pain syndrome, compression neuropathy,congenital facial diplegia, corticobasal degeneration, cranialarteritis, craniosynostosis, Creutzfeldt-Jakob disease, cumulativetrauma disorder, Cushing's syndrome, cytomegalic inclusion body disease(CIBD), Dandy-Walker syndrome, Dawson disease, de Morsier's syndrome,Dejerine-Klumpke palsy, Dejerine-Sottas disease, delayed sleep phasesyndrome, dementia, dermatomyositis, developmental dyspraxia, diabeticneuropathy, diffuse sclerosis, Dravet syndrome, dysautonomia,dyscalculia, dysgraphia, dyslexia, dystonia, empty sella syndrome,encephalitis, encephalocele, encephalotrigeminal angiomatosis,encopresis, epilepsy, Erb's palsy, erythromelalgia, essential tremor,Fabry's disease, Fahr's syndrome, familial spastic paralysis, febrileseizure, Fisher syndrome, Friedreich's ataxia, fibromyalgia, Foville'ssyndrome, Gaucher's disease, Gerstmann's syndrome, giant cell arteritis,giant cell inclusion disease, globoid cell leukodystrophy, gray matterheterotopia, Guillain-Barre syndrome, HTLV-1 associated myelopathy,Hallervorden-Spatz disease, hemifacial spasm, hereditary spasticparaplegia, heredopathia atactica polyneuritiformis, herpes zosteroticus, herpes zoster, Hirayama syndrome, holoprosencephaly,Huntington's disease, hydranencephaly, hydrocephalus, hypercortisolism,hypoxia, immune-mediated encephalomyelitis, inclusion body myositis,incontinentia pigmenti, infantile phytanic acid storage disease,infantile Refsum disease, infantile spasms, inflammatory myopathy,intracranial cyst, intracranial hypertension, Joubert syndrome, Karaksyndrome, Kearns-Sayre syndrome, Kennedy disease, Kinsbourne syndrome,Klippel Feil syndrome, Krabbe disease, Kugelberg-Welander disease, kuru,Lafora disease, Lambert-Eaton myasthenic syndrome, Landau-Kleffnersyndrome, lateral medullary (Wallenberg) syndrome, Leigh's disease,Lennox-Gastaut syndrome, Lesch-Nyhan syndrome, leukodystrophy, Lewy bodydementia, lissencephaly, locked-in syndrome, Lou Gehrig's disease,lumbar disc disease, lumbar spinal stenosis, Lyme disease,Machado-Joseph disease (Spinocerebellar ataxia type 3), macrencephaly,macropsia, megalencephaly, Melkersson-Rosenthal syndrome, Meniere'sdisease, meningitis, Menkes disease, metachromatic leukodystrophy,microcephaly, micropsia, Miller Fisher syndrome, misophonia,mitochondrial myopathy, Mobius syndrome, monomelic amyotrophy, motorneuron disease, motor skills disorder, Moyamoya disease,mucopolysaccharidoses, multi-infarct dementia, multifocal motorneuropathy, multiple sclerosis, multiple system atrophy, musculardystrophy, myalgic encephalomyelitis, myasthenia gravis, myelinoclasticdiffuse sclerosis, myoclonic Encephalopathy of infants, myoclonus,myopathy, myotubular myopathy, myotonia congenital, narcolepsy,neurofibromatosis, neuroleptic malignant syndrome, lupus erythematosus,neuromyotonia, neuronal ceroid lipofuscinosis, Niemann-Pick disease,O'Sullivan-McLeod syndrome, occipital Neuralgia, occult SpinalDysraphism Sequence, Ohtahara syndrome, olivopontocerebellar atrophy,opsoclonus myoclonus syndrome, optic neuritis, orthostatic hypotension,palinopsia, paresthesia, Parkinson's disease, paramyotonia Congenita,paraneoplastic diseases, paroxysmal attacks, Parry-Romberg syndrome,Pelizaeus-Merzbacher disease, periodic paralyses, peripheral neuropathy,photic sneeze reflex, phytanic acid storage disease, Pick's disease,polymicrogyria (PMG), polymyositis, porencephaly, post-polio syndrome,postherpetic neuralgia (PHN), postural hypotension, Prader-Willisyndrome, primary lateral sclerosis, prion diseases, progressivehemifacial atrophy, progressive multifocal leukoencephalopathy,progressive supranuclear palsy, pseudotumor cerebri, Ramsay Huntsyndrome type I, Ramsay Hunt syndrome type II, Ramsay Hunt syndrome typeIII, Rasmussen's encephalitis, reflex neurovascular dystrophy, Refsumdisease, restless legs syndrome, retrovirus-associated myelopathy, Rettsyndrome, Reye's syndrome, rhythmic movement disorder, Romberg syndrome,Saint Vitus dance, Sandhoff disease, schizophrenia, Schilder's disease,schizencephaly, sensory integration dysfunction, septo-optic dysplasia,Shy-Drager syndrome, Sjögren's syndrome, snatiation, Sotos syndrome,spasticity, spina bifida, spinal cord tumors, spinal muscular atrophy,spinocerebellar ataxia, Steele-Richardson-Olszewski syndrome,Stiff-person syndrome, stroke, Sturge-Weber syndrome, subacutesclerosing panencephalitis, subcortical arteriosclerotic encephalopathy,superficial siderosis, Sydenham's chorea, syncope, synesthesia,syringomyelia, tarsal tunnel syndrome, tardive dyskinesia, tardivedysphrenia, Tarlov cyst, Tay-Sachs disease, temporal arteritis, tetanus,tethered spinal cord syndrome, Thomsen disease, thoracic outletsyndrome, tic douloureux, Todd's paralysis, Tourette syndrome, toxicencephalopathy, transient ischemic attack, transmissible spongiformencephalopathies, transverse myelitis, tremor, trigeminal neuralgia,tropical spastic paraparesis, trypanosomiasis, tuberous sclerosis,ubisiosis, Von Hippel-Lindau disease (VHL), Viliuisk Encephalomyelitis(VE), Wallenberg's syndrome, Werdnig, Hoffman disease, west syndrome,Williams syndrome, Wilson's disease and Zellweger syndrome.

The compounds and compositions may also be useful in the inhibition ofthe development of invasive cancer, tumor angiogenesis and metastasis.

In some embodiments, the disclosure provides a method for treating adisease or disorder associated with aberrant cellular proliferation byadministering to a patient in need of such treatment an effective amountof one or more of the compounds of Formula (I), in combination(simultaneously or sequentially) with at least one other agent.

In some embodiments, the disclosure provides a method of treating orameliorating in a patient a disorder or disease selected from the groupconsisting of: cancer, pulmonary fibrosis, idiopathic pulmonary fibrosis(IPF), degenerative disc disease, bone/osteoporotic fractures, bone orcartilage disease, and osteoarthritis, the method comprisingadministering to the patient a therapeutically effective amount of acompound according to claim 1, or a pharmaceutically acceptable saltthereof.

In some embodiments, the pharmaceutical composition comprises atherapeutically effective amount of a compound of Formula (I), or apharmaceutically acceptable salt thereof, and a pharmaceuticallyacceptable excipient.

In some embodiments, the method of treats a disorder or disease in whichaberrant Wnt signaling is implicated in a patient, the method comprisesadministering to the patient a therapeutically effective amount of acompound of Formula (I), or a pharmaceutically acceptable salt thereof.

In some embodiments, the disorder or disease is cancer.

In some embodiments, the disorder or disease is systemic inflammation.

In some embodiments, the disorder or disease is metastatic melanoma.

In some embodiments, the disorder or disease is fatty liver disease.

In some embodiments, the disorder or disease is liver fibrosis.

In some embodiments, the disorder or disease is tendonitis.

In some embodiments, the disorder or disease is damage to a tendonrequiring tendon regeneration.

In some embodiments, the disorder or disease is diabetes.

In some embodiments, the disorder or disease is degenerative discdisease.

In some embodiments, the disorder or disease is osteoarthritis.

In some embodiments, the disorder or disease is diabetic retinopathy.

In some embodiments, the disorder or disease is pulmonary fibrosis.

In some embodiments, the disorder or disease is idiopathic pulmonaryfibrosis (IPF).

In some embodiments, the disorder or disease is degenerative discdisease.

In some embodiments, the disorder or disease is rheumatoid arthritis.

In some embodiments, the disorder or disease is scleroderma.

In some embodiments, the disorder or disease is a mycotic or viralinfection.

In some embodiments, the disorder or disease is a bone or cartilagedisease.

In some embodiments, the disorder or disease is Alzheimer's disease.

In some embodiments, the disorder or disease is osteoarthritis.

In some embodiments, the disorder or disease is lung disease

In some embodiments, the disorder or disease is a genetic disease causedby mutations in Wnt signaling components, wherein the genetic disease isselected from: polyposis coli, osteoporosis-pseudoglioma syndrome,familial exudative vitreoretinopathy, retinal angiogenesis, earlycoronary disease, tetra-amelia syndrome, Müllerian-duct regression andvirilization, SERKAL syndrome, diabetes mellitus type 2, Fuhrmannsyndrome, Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome,odonto-onycho-dermal dysplasia, obesity, split-hand/foot malformation,caudal duplication syndrome, tooth agenesis, Wilms tumor, skeletaldysplasia, focal dermal hypoplasia, autosomal recessive anonychia,neural tube defects, alpha-thalassemia (ATRX) syndrome, fragile Xsyndrome, ICF syndrome, Angelman syndrome, Prader-Willi syndrome,Beckwith-Wiedemann Syndrome, Norrie disease and Rett syndrome.

In some embodiments, the patient is a human.

In some embodiments, the cancer is chosen from: hepatocellularcarcinoma, colon cancer, breast cancer, pancreatic cancer, chronicmyeloid leukemia (CML), chronic myelomonocytic leukemia, chroniclymphocytic leukemia (CLL), acute myeloid leukemia, acute lymphocyticleukemia, Hodgkin lymphoma, lymphoma, sarcoma and ovarian cancer.

In some embodiments, the cancer is chosen from: lung cancer—non-smallcell, lung cancer—small cell, multiple myeloma, nasopharyngeal cancer,neuroblastoma, osteosarcoma, penile cancer, pituitary tumors, prostatecancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, skincancer—basal and squamous cell, skin cancer—melanoma, small intestinecancer, stomach (gastric) cancers, testicular cancer, thymus cancer,thyroid cancer, uterine sarcoma, vaginal cancer, vulvar cancer,laryngeal or hypopharyngeal cancer, kidney cancer, Kaposi sarcoma,gestational trophoblastic disease, gastrointestinal stromal tumor,gastrointestinal carcinoid tumor, gallbladder cancer, eye cancer(melanoma and lymphoma), Ewing tumor, esophagus cancer, endometrialcancer, colorectal cancer, cervical cancer, brain or spinal cord tumor,bone metastasis, bone cancer, bladder cancer, bile duct cancer, analcancer and adrenal cortical cancer.

In some embodiments, the cancer is hepatocellular carcinoma.

In some embodiments, the cancer is colon cancer.

In some embodiments, the cancer is colorectal cancer.

In some embodiments, the cancer is breast cancer.

In some embodiments, the cancer is pancreatic cancer.

In some embodiments, the cancer is chronic myeloid leukemia (CML).

In some embodiments, the cancer is chronic myelomonocytic leukemia.

In some embodiments, the cancer is chronic lymphocytic leukemia (CLL).

In some embodiments, the cancer is acute myeloid leukemia.

In some embodiments, the cancer is acute lymphocytic leukemia.

In some embodiments, the cancer is Hodgkin lymphoma.

In some embodiments, the cancer is lymphoma.

In some embodiments, the cancer is sarcoma.

In some embodiments, the cancer is ovarian cancer.

In some embodiments, the cancer is lung cancer—non-small cell.

In some embodiments, the cancer is lung cancer—small cell.

In some embodiments, the cancer is multiple myeloma.

In some embodiments, the cancer is nasopharyngeal cancer.

In some embodiments, the cancer is neuroblastoma.

In some embodiments, the cancer is osteosarcoma.

In some embodiments, the cancer is penile cancer.

In some embodiments, the cancer is pituitary tumors.

In some embodiments, the cancer is prostate cancer.

In some embodiments, the cancer is retinoblastoma.

In some embodiments, the cancer is rhabdomyosarcoma.

In some embodiments, the cancer is salivary gland cancer.

In some embodiments, the cancer is skin cancer—basal and squamous cell.

In some embodiments, the cancer is skin cancer—melanoma.

In some embodiments, the cancer is small intestine cancer.

In some embodiments, the cancer is stomach (gastric) cancers.

In some embodiments, the cancer is testicular cancer.

In some embodiments, the cancer is thymus cancer.

In some embodiments, the cancer is thyroid cancer.

In some embodiments, the cancer is uterine sarcoma.

In some embodiments, the cancer is vaginal cancer.

In some embodiments, the cancer is vulvar cancer.

In some embodiments, the cancer is Wilms tumor.

In some embodiments, the cancer is laryngeal or hypopharyngeal cancer.

In some embodiments, the cancer is kidney cancer.

In some embodiments, the cancer is Kaposi sarcoma.

In some embodiments, the cancer is gestational trophoblastic disease.

In some embodiments, the cancer is gastrointestinal stromal tumor.

In some embodiments, the cancer is gastrointestinal carcinoid tumor.

In some embodiments, the cancer is gallbladder cancer.

In some embodiments, the cancer is eye cancer (melanoma and lymphoma).

In some embodiments, the cancer is Ewing tumor.

In some embodiments, the cancer is esophagus cancer.

In some embodiments, the cancer is endometrial cancer.

In some embodiments, the cancer is colorectal cancer.

In some embodiments, the cancer is cervical cancer.

In some embodiments, the cancer is brain or spinal cord tumor.

In some embodiments, the cancer is bone metastasis.

In some embodiments, the cancer is bone cancer.

In some embodiments, the cancer is bladder cancer.

In some embodiments, the cancer is bile duct cancer.

In some embodiments, the cancer is anal cancer.

In some embodiments, the cancer is adrenal cortical cancer.

In some embodiments, the disorder or disease is a neurologicalcondition, disorder or disease, wherein the neurologicalcondition/disorder/disease is selected from: Alzheimer's disease,frontotemporal dementias, dementia with lewy bodies, prion diseases,Parkinson's disease, Huntington's disease, progressive supranuclearpalsy, corticobasal degeneration, multiple system atrophy, amyotrophiclateral sclerosis (ALS), inclusion body myositis, autism, degenerativemyopathies, diabetic neuropathy, other metabolic neuropathies, endocrineneuropathies, orthostatic hypotension, multiple sclerosis andCharcot-Marie-Tooth disease.

In some embodiments, the compound of Formula (I) inhibits one or moreproteins in the Wnt pathway.

In some embodiments, the compound of Formula (I) inhibits signalinginduced by one or more Wnt proteins.

In some embodiments, the Wnt proteins are chosen from: WNT1, WNT2,WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A,WNT8B, WNT9A, WNT9B, WNT10A, WNT10B, WNT11, and WNT16.

In some embodiments, the method inhibits one or more proteins in the Wntpathway, the method comprises contacting a cell with an effective amountof a compound of Formula (I).

In some embodiments, the cell is a human cell.

In some embodiments, the human cell is a cancerous cell.

In some embodiments, the cancerous cell is a colon cancer cell.

In some embodiments, the contacting is in vitro.

In some embodiments, the compound of Formula (I) inhibits a kinaseactivity.

In some embodiments, the method treats a disease or disorder mediated bythe Wnt pathway in a patient, the method comprises administering to thepatient a therapeutically effective amount of a compound (or compounds)of Formula (I), or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) inhibits one or moreWnt proteins.

In some embodiments, the method treats a disease or disorder mediated bykinase activity in a patient, the method comprises administering to thepatient a therapeutically effective amount of a compound (or compounds)of Formula (I), or a pharmaceutically acceptable salt thereof.

In some embodiments, the disease or disorder comprises tumor growth,cell proliferation, or angiogenesis.

In some embodiments, the method inhibits the activity of a proteinkinase receptor, the method comprises contacting the receptor with aneffective amount of a compound (or compounds) of Formula (I), or apharmaceutically acceptable salt thereof.

In some embodiments, the method treats a disease or disorder associatedwith aberrant cellular proliferation in a patient; the method comprisesadministering to the patient a therapeutically effective amount of acompound (or compounds) of Formula (I), or a pharmaceutically acceptablesalt thereof.

In some embodiments, the method prevents or reduces angiogenesis in apatient; the method comprises administering to the patient atherapeutically effective amount of a compound (or compounds) of Formula(I), or a pharmaceutically acceptable salt thereof.

In some embodiments, the method prevents or reduces abnormal cellularproliferation in a patient; the method comprises administering to thepatient a therapeutically effective amount of a compound (or compounds)of Formula (I), or a pharmaceutically acceptable salt thereof.

In some embodiments, the method treats a disease or disorder associatedwith aberrant cellular proliferation in a patient, the method comprisesadministering to the patient a pharmaceutical composition comprising oneor more of the compounds of claim 1 in combination with apharmaceutically acceptable carrier and one or more other agents.

Moreover, the compounds and compositions, for example, as inhibitors ofthe cyclin-dependent kinases (CDKs), can modulate the level of cellularRNA and DNA synthesis and therefore are expected to be useful in thetreatment of viral infections such as HIV, human papilloma virus, herpesvirus, Epstein-Barr virus, adenovirus, Sindbis virus, pox virus and thelike.

Compounds and compositions described herein can inhibit the kinaseactivity of, for example, CDK/cyclin complexes, such as those active inthe G_(0.) or G_(.1) stage of the cell cycle, e.g., CDK2, CDK4, and/orCDK6 complexes.

Evaluation of Biological Activity

The biological activity of the compounds described herein can be testedusing any suitable assay known to those of skill in the art, see, e.g.,WO 2001/053268 and WO 2005/009997. For example, the activity of acompound may be tested using one or more of the test methods outlinedbelow.

In one example, tumor cells may be screened for Wnt independent growth.In such a method, tumor cells of interest are contacted with a compound(i.e. inhibitor) of interest, and the proliferation of the cells, e.g.by uptake of tritiated thymidine, is monitored. In some embodiments,tumor cells may be isolated from a candidate patient who has beenscreened for the presence of a cancer that is associated with a mutationin the Wnt signaling pathway. Candidate cancers include, withoutlimitation, those listed above.

In another example, one may utilize in vitro assays for Wnt biologicalactivity, e.g. stabilization of β-catenin and promoting growth of stemcells. Assays for biological activity of Wnt include stabilization ofβ-catenin, which can be measured, for example, by serial dilutions of acandidate inhibitor composition. An exemplary assay for Wnt biologicalactivity contacts a candidate inhibitor with cells containingconstitutively active Wnt/β-catenin signaling. The cells are culturedfor a period of time sufficient to stabilize β-catenin, usually at leastabout 1 hour, and lysed. The cell lysate is resolved by SDS PAGE, thentransferred to nitrocellulose and probed with antibodies specific forβ-catenin.

In a further example, the activity of a candidate compound can bemeasured in a Xenopus secondary axis bioassay (Leyns, L. et al. Cell(1997), 88(6), 747-756).

To further illustrate this invention, the following examples areincluded. The examples should not, of course, be construed asspecifically limiting the invention. Variations of these examples withinthe scope of the claims are within the purview of one skilled in the artand are considered to fall within the scope of the invention asdescribed, and claimed herein. The reader will recognize that theskilled artisan, armed with the present disclosure, and skill in the artis able to prepare and use the invention without exhaustive examples.

EXAMPLES

Compound Preparation

The starting materials used in preparing the compounds of the inventionare known, made by known methods, or are commercially available. It willbe apparent to the skilled artisan that methods for preparing precursorsand functionality related to the compounds claimed herein are generallydescribed in the literature. The skilled artisan given the literatureand this disclosure is well equipped to prepare any of the compounds.

It is recognized that the skilled artisan in the art of organicchemistry can readily carry out manipulations without further direction,that is, it is well within the scope and practice of the skilled artisanto carry out these manipulations. These include reduction of carbonylcompounds to their corresponding alcohols, oxidations, acylations,aromatic substitutions, both electrophilic and nucleophilic,etherifications, esterification and saponification and the like. Thesemanipulations are discussed in standard texts such as March's AdvancedOrganic Chemistry: Reactions, Mechanisms, and Structure 7^(th) Ed., JohnWiley & Sons (2013), Carey and Sundberg, Advanced Organic Chemistry5^(th) Ed., Springer (2007), Comprehensive Organic Transformations: AGuide to Functional Group Transformations, 2^(nd) Ed., John Wiley & Sons(1999) (incorporated herein by reference in its entirety) and the like.

The skilled artisan will readily appreciate that certain reactions arebest carried out when other functionality is masked or protected in themolecule, thus avoiding any undesirable side reactions and/or increasingthe yield of the reaction. Often the skilled artisan utilizes protectinggroups to accomplish such increased yields or to avoid the undesiredreactions. These reactions are found in the literature and are also wellwithin the scope of the skilled artisan. Examples of many of thesemanipulations can be found for example in T. Greene and P. WutsProtective Groups in Organic Synthesis, 4th Ed., John Wiley & Sons(2007), incorporated herein by reference in its entirety.

Trademarks used herein are examples only and reflect illustrativematerials used at the time of the invention. The skilled artisan willrecognize that variations in lot, manufacturing processes, and the like,are expected. Hence the examples, and the trademarks used in them arenon-limiting, and they are not intended to be limiting, but are merelyan illustration of how a skilled artisan may choose to perform one ormore of the embodiments of the invention.

(¹H) nuclear magnetic resonance spectra (NMR) were measured in theindicated solvents on a Bruker NMR spectrometer (Avance™ DRX300, 300 MHzfor ¹H or Avance™ DRX500, 500 MHz for ¹H) or Varian NMR spectrometer(Mercury 400BB, 400 MHz for ¹H). Peak positions are expressed in partsper million (ppm) downfield from tetramethylsilane. The peakmultiplicities are denoted as follows, s, singlet; d, doublet; t,triplet; q, quartet; ABq, AB quartet; quin, quintet; sex, sextet; sep,septet; non, nonet; dd, doublet of doublets; ddd, doublet of doublets ofdoublets; d/ABq, doublet of AB quartet; dt, doublet of triplets; td,triplet of doublets; dq, doublet of quartets; m, multiplet.

The following abbreviations have the indicated meanings:

BH₃-Me₂S=borane dimethyl sulfide complex

(Boc)₂O=di-tert-butyl dicarbonate

brine=saturated aqueous sodium chloride

CDCl₃=deuterated chloroform

CD₃OD=deuterated methanol

DCAD=di-(4-chlorobenzyl)azodicarboxylate

DCE=dichloroethane

DCM=dichloromethane

DEAD=diethyl azodicarboxylate

DHP=dihydropyran

DMAP=4-dimethylaminopyridine

DMF=N,N-dimethylformamide

DMSO-d₆=deuterated dimethylsulfoxide

ESIMS=electron spray mass spectrometry

EtOAc=ethyl acetate

EtOH=ethanol

HCl=hydrochloric acid

HOAc=acetic acid

K₂CO₃=potassium carbonate

KOAc=potassium acetate

LC/MS=liquid chromatography-mass spectrometry

MeOH=methanol

MgSO₄=magnesium sulfate

MsCl=methanesulfonyl chloride or mesyl chloride

MW=microwave

NaBH₄=sodium borohydride

NaBH(OAc)₃=sodium triacetoxyborohydride

NaCNBH₃=sodium cyanoborohydride

NaHCO₃=sodium bicarbonate

NaOH=sodium hydroxide

Na₂S₂O₅=sodium metabisulfite or sodium pyrosulfite

NBS=N-bromosuccinimide

NH₄OH=ammonium hydroxide

NMR=nuclear magnetic resonance

ON=overnight

Pd/C=palladium(0) on carbon

Pd(dppf)Cl₂=1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride

Pd(PPh₃)₄=tetrakis(triphenylphosphine)palladium(0)

Pd(PPh₃)₂Cl₂=bis(triphenylphosphine)palladium(II) dichloride

PE=petroleum ether

Pin₂B₂=bis(pinacolato)diboron

PPh₃=triphenylphosphine

PPTS=pyridinium p-toluenesulfonate

r.t.=room temperature

SEM-Cl=2-(trimethylsilyl)ethoxymethyl chloride

TBME=methyl tert-butyl ether

TEA=triethylamine

TFA=trifluoroacetic acid

THF=tetrahydrofuran

THP=tetrahydropyran

TLC=thin layer chromatography

p-TsOH=p-toluenesulfonic acid

The following example schemes are provided for the guidance of thereader, and collectively represent an example method for making thecompounds provided herein. Furthermore, other methods for preparingcompounds of the invention will be readily apparent to the person ofordinary skill in the art in light of the following reaction schemes andexamples. The skilled artisan is thoroughly equipped to prepare thesecompounds by those methods given the literature and this disclosure. Thecompound numberings used in the synthetic schemes depicted below aremeant for those specific schemes only, and should not be construed as orconfused with same numberings in other sections of the application.Unless otherwise indicated, all variables are as defined above.

General Procedure

Compounds of Formula (I) of the present invention can be prepared asdepicted in Scheme 1.

Scheme 1 describes an alternative method for preparation of indazolederivatives (X) by first formylating 5-bromo-1H-indole (II) to produce5-bromo-1H-indazole-3-carbaldehyde (III) followed by protection witheither SEM-Cl or DHP to give the protected aldehyde (IV). Aldehyde (IV)is then reacted with bis(pinacolato)diboron to form the borate ester(V). Suzuki coupling with various bromides (VI) yields indazolederivatives (VII). Aldehyde (VII) is reacted with various 1,2-diamines(VIII) to produce (IX). Final deprotection of the pyrazole nitrogenyields the desired indazole derivatives (X).

Illustrative Compound Examples

Preparation of SEM protected intermediate (XIV) is depicted below inScheme 2.

Step 1

A solution of NaNO₂ (110.4 g, 1.6 mol, 8 eq) in water (200 mL) was addeddropwise to a solution of 5-bromoindole (XI) (39.2 g, 0.2 mol, 1 eq) inacetone (1000 mL) stirred at −10→0° C., while adding NaNO₂ the solutiontemperature was maintained below 20° C. An aqueous 2N HCl solution (480mL) was added slowly to the solution with vigorously stirring whilekeeping the internal temperature between 0 and 20° C. The solution wasfurther stirred at 20° C. for 3 h after the addition. The solution wasconcentrated under reduced pressure to remove acetone while keeping thetemperature below 35° C. The solid was collected by filtration andtransferred to a flask. Cold (−10° C.) DCM (200 mL) was added andstirred for 30 min at −5° C., the solids were filtered and dried undervacuum at 40° C. to get 5-bromo-1H-indazole-3-carbaldehyde (XII) (34.0g, 151 mmol, 76% yield) as a brown solid. ESIMS found for C₈H₅BrN₂O m/z225 (M+H).

Step 2

To a suspension of NaH (6.6 g, 166 mmol, 1.10 eq) in DMF (500 mL) wasadded a solution of 5-bromo-1H-indazole-3-carbaldehyde (XII) (34.0 g,151 mmol, 1.0 eq) in DMF (50 mL) dropwise at 0° C. over a period of 30min. The mixture was stirred at room temperature for 2 h, then SEM-Cl(26.4 g, 159 mmol, 1.08 eq) was added dropwise and the mixture wasstirred at room temperature for another 3 h. Then the mixture was pouredinto an ice-water mixture (1000 mL) and extracted with EtOAc (300 mL×3),the organic phases were combined, dried over Na₂SO₄, filtered andconcentrated in vacuo, the resultant residue was purified by flashchromatography on silica gel (PE:EtOAc=20:1→10:1) to afford5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carbaldehyde(XIII) as a mixture of regioisomers (53.0 g, 151 mmol, 100% yield) as ayellow oil. ESIMS found for C₁₄H₁₉BrN₂O₂Si m/z 355 (M+H).

Step 3

To a solution of the mixed 5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carbaldehyde (XIII) (53.0 g, 151 mmol, 1.0 eq),bis(pinacolato)diboron (38.0 g, 150 mmol, 1.0 eq) and KOAc (44.0 g, 450mmol, 3.0 eq) in DMF (1000 mL) was added Pd(dppf)Cl₂ (7.7 g, 10.5 mmol,0.07 eq). The mixture was stirred at 90° C. under nitrogen for 10 h. Themixture was filtered; the filtrate was poured onto water (1000 mL) andextracted with EtOAc (500 mL×3). The combined organic phases were dried,filtered and concentrated in vacuo. The resultant residue was purifiedby flash chromatography on silica gel (PE:EtOAc=10:1→1:1) to give the5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-H-indazole-3-carbaldehyde(XIV) as a mixture of regioisomers (42.9 g, 106 mmol, 71% yield) as ayellow oil. ESIMS found for C₂₀H₃₁BN₂O₄Si m/z 403 (M+H).

Preparation of THP protected intermediate (XV) is depicted below inScheme 3.

Step 1

Procedure can be found in Scheme 2, Step 1.

Step 2

A mixture of 5-bromo-1H-indazole-3-carbaldehyde (XII) (29.9 g, 133mmol), 3,4-dihydro-2H-pyran (27.4 mL, 300 mmol) and PPTS (352 mg, 1.4mmol) in DCM was heated to reflux for 5 hours. The solution was pouredinto a saturated NaHCO₃ solution, the layers were separated, and theaqueous layer was extracted with DCM. The combined organic layers werewashed with 5% aqueous citric acid and brine, dried over MgSO₄, andconcentrated. The crude product was purified on a silica gel column(100% EtOAc→3:97 MeOH:DCM) to provide5-bromo-1-(tetrahydro-2H-pyran-2-yl)-3a,7a-dihydro-1H-indazole-3-carbaldehyde(XV) was isolated as a white solid (16.4 g, 52.7 mmol, 39.6% yield). ¹HNMR (DMSO-d₆, 500 MHz) δ ppm 1.57-1.65 (m, 2H), 1.72-1.83 (m, 1H),2.02-2.11 (m, 2H), 2.33-2.44 (m 1H), 3.76-3.83 (m, 1H), 3.84-3.93 (m,1H), 6.08 (dd, J=2.5 Hz, 9 Hz, 1H), 7.72 (dd, J=1.5 Hz, J=8.5 Hz, 1H),7.92 (d, J=9 Hz, 1H), 8.28 (d, J=2 Hz, 1H), 10.17 (s, 1H); ESIMS foundC₁₃H₁₅BrN₂O₂ m/z 311.0 (M+H).

Preparation of 6-fluoro-substituted indazole intermediate (XXII) isdepicted below in Scheme 4.

Step 1

A solution of 5-fluoro-2-methylaniline (XVI) (100 g, 799 mmol, 1.0 eq)and Ac₂O (89 g, 879 mmol, 1.1 eq) in toluene (4.0 L) was stirred at 110°C. for 4 h. TLC (PE:EtOAc=2:1) showed (XVI) was consumed. The reactionmixture was cooled to 25° C. The precipitated solid was filtered, washedwith petro ether. The solid was dried in vacuo to giveN-(5-fluoro-2-methylphenyl)acetamide (XVII) as a white solid (120 g,717.8 mmol, 89.8% yield), which was used in step 2 without furtherpurification. ESIMS found C₉H₁₀FNO m/z 168.1 (M+1).

Step 2

To a solution of N-(5-fluoro-2-methylphenyl)acetamide (XVII) (120 g, 717mmol, 1.0 eq) in HOAc (3 L) was added a solution of Br₂ (140 g, 876mmol, 1.2 eq) in HOAc (1 L) dropwise. The mixture was stirred at 25° C.for 3 h. LC/MS showed compound 2 was (XVII) completely consumed. Thereaction mixture was quenched with water (8 L). The solid was filtered,washed with water and petroleum ether. The solid was dried in vacuo togive N-(4-bromo-5-fluoro-2-methylphenyl)acetamide (XVIII) as a whitesolid (155 g, 629.9 mmol, 87.8% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm2.20 (s, 6H), 7.07 (brs, 1H), 7.32 (d, J=7.2 Hz, 1H), 7.85 (d, J=10.8Hz, 1H); ESIMS found C₉H₉BrFNO m/z 247.2 (M+1).

Step 3

A solution of N-(4-bromo-5-fluoro-2-methylphenyl)acetamide (XVIII) (155g, 629.9 mmol, 1.0 eq), Ac₂O (192 g, 1.8 mol, 3.0 eq), KOAc (123 g, 1.26mol, 2.0 eq), 18-CROWN-6 (8.3 g, 31 mmol, 0.05 eq) and isoamyl nitrite(147 g, 1.2 mol, 2.0 eq) in CHCl₃ (7.0 L) was stirred at 65° C. for 12h. TLC (PE:EtOAc=5:1, Rf=0.2) showed (XVIII) was consumed completely.The solvent was removed under reduced pressure. The residue wasextracted with EtOAc (1.5 L) and water (1.5 L). The organic layer wasdried over anhydrous Na₂SO₄, concentrated under reduced pressure to give1-(5-bromo-6-fluoro-1H-indazol-1-yl)ethan-1-one (XIX) as a white solid(170 g, crude, quantitative yield), which was used in step 4 withoutfurther purification. ESIMS found C₉H₆BrFN₂O m/z 258.1 (M+1).

Step 4

A solution of 1-(5-bromo-6-fluoro-1H-indazol-1-yl)ethan-1-one (XIX) (170g, 629.9 mmol, 1.0 eq) in 3 N HCl (6.6 mol, 10 eq) and MeOH (900 mL) wasstirred at 60° C. for 12 h. TLC (PE:EtOAc=5:1, Rf=0.8) showed (XIX) wasconsumed completely. The reaction mixture was cooled to room temperatureand basified with 1N aq. NaOH to pH=10. The precipitated solid wasfiltered and dried in vacuo to afford 5-bromo-6-fluoro-1H-indazole (XX)as a yellow solid (100 g, 465.1 mmol, 73.8% yield). ESIMS foundC₇H₄BrFN₂ m/z 215.1 (M+1).

Step 5

To solution of a mixture of 5-bromo-6-fluoro-1H-indazole (XX) (90 g, 418mmol, 1.0 eq) and 3,4-dihydro-2H-pyran (70 g, 837 mmol, 2.0 eq) in DCM(2.0 L) was added p-TsOH (3.6 g, 20 mmol, 0.05 eq) at 25° C. Theresulting mixture was stirred at 25° C. for 12 h. TLC (PE:EtOAc=5:1,Rf=0.7) showed (XX) was completely consumed. To the reaction mixture wasadded saturated aqueous NaHCO₃ (4 L). The organic layer was separated,dried over Na₂SO₄, concentrated in vacuo to give a residue, which wasfurther purified by silica gel column (EtOAc:PE=20:1) to give5-bromo-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (XXI) as abrown oil (120 g, 401.1 mmol, 96.0% yield), which was used in step 6without further purification. ESIMS found C₁₂H₁₂BrFN₂O m/z 299.2 (M+1).

Step 6

A solution of 5-bromo-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole(XXI) (30 g, 100 mmol, 1.0 eq),4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane(25 g, 100 mmol, 1.0 eq), Pd(dppf)Cl₂ (3.6 g, 5.0 mmol, 0.05 eq), KOAc(19.6 g, 200 mmol, 2.0 eq) in dioxane (550 mL) was stirred at 100° C.for 12 h under N₂. LC/MS showed (XXI) was completely consumed. Thereaction mixture was concentrated and then extracted with EtOAc (300 mL)and water (100 mL). The mixture was filtered and separated. The organiclayer was dried over anhydrous Na₂SO₄, concentrated to give crudeproduct, which was further purified by silica gel column (EtOAc:PE=20/1)to give6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole(XXII) as a green solid (13 g, 37.5 mmol, 37.4% yield). ¹H NMR (CDCl₃,400 MHz) δ ppm 1.37 (s, 12H), 1.73-1.43 (m, 3H), 2.58-2.50 (m, 1H),3.79-3.73 (m, 1H), 4.06-4.04 (m, 1H), 5.66-5.63 (m, 1H), 7.28-7.21 (m,1H), 8.00 (s, 1H), 8.19 (d, J=5.6 Hz, 1H); ESIMS found C₁₈H₂₄BFN₂O₃ m/z347.2 (M+1).

Preparation of 7-fluoro-substituted indazole intermediate (XXVIII) isdepicted below in Scheme 5.

Step 1

To a stirred solution of 2,3-difluorobenzaldehyde (XXIII) (75.0 g, 528mmol, 1.0 eq) in H₂SO₄ (565 mL) was added NBS (113 g, 633 mmol, 1.2 eq)in portions at 60° C. The resulting mixture was stirred at 60° C. for 12hr. LC/MS showed the reaction was completed. The reaction mixture waspoured into ice water and petroleum ether (500 mL) and stirred for 10min, the organic layer was separated and concentrated under vacuum togive crude product. The residue was purified column chromatographysilica gel (100% petroleum ether) to give5-bromo-2,3-difluorobenzaldehyde (XXIV) (120 g, 543.0 mmol, quantitativeyield). ESIMS found C₇H₃BrF₂O m/z 221.1 (M+1).

Step 2

To a solution of 5-bromo-2,3-difluorobenzaldehyde (XXIV) (115 g, 520mmol, 1.0 eq), MeONH₂—HCl (47.8 g, 572 mmol, 1.1 eq) and K₂CO₃ (86.3 g,624 mmol, 1.20 eq) was in DME (1.30 L) was heated to 40° C. for 15 h.TLC (petroleum ether) showed (XXIV) was consumed. The reaction wasfiltered and the filtrate was concentrated under vacuum to give crudeproduct. The residue was purified by column chromatography on silica gel(100% petroleum ether) to give (E)-5-bromo-2,3-difluorobenzaldehydeO-methyl oxime (XXV) (74 g, 56.9% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm4.04 (s, 3H), 7.37-7.32 (m, 1H), 7.77 (s, 1H), 8.23 (s, 1H); ESIMS foundC₈H₆BrF₂NO m/z 250.2 (M+1).

Step 3

A solution of (E)-5-bromo-2,3-difluorobenzaldehyde O-methyl oxime (XXV)(150 g, 600 mmol, 1.0 eq), NH₂NH₂.H₂O (600 mL) in dry THF (600 mL) washeated to 90° C. for 84 h. LC/MS showed the reaction was completed. Thesolvent was evaporated and the resulting mixture was diluted with EtOAc,washed with water, dried over Na₂SO₄ and concentrated under vacuum togive crude product. The residue was purified by column chromatography onsilica gel (PE:EtOAc=10:1) to give 5-bromo-7-fluoro-1H-indazole (XXVI)as a white solid (78 g, 362.7 mmol, 60.5% yield). ¹H NMR (DMSO-d₆, 400MHz) δ ppm 7.44 (d, J=9.6 Hz, 1H), 7.87 (d, J=1.6 Hz, 1H), 8.17 (s, 1H),13.90 (s, 1H); ESIMS found C₇H₄BrFN₂ m/z 215 (M+1).

Step 4

Preparation of 5-bromo-7-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole(XXVII) was performed following the procedure listed in Scheme 4, Step5. Light yellow solid (98 g, 327.6 mmol, 93.9% yield). ¹H NMR (CDCl₃,400 MHz) δ ppm 1.78-1.62 (m, 3H), 2.17-2.09 (m, 2H), 2.63-2.58 (m, 1H),3.76 (t, J=11.6 Hz, 1H), 4.05 (d, J=9.6 Hz, 1H), 5.85 (d, J=9.6 Hz, 1H),7.22 (d, J=12.0 Hz, 1H), 7.65 (s, 1H), 8.00 (s, 1H); ESIMS foundC₁₂H₁₂BrFN₂O m/z 299.2 (M+1).

Step 5

Preparation of7-fluoro-1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole(XXVIII) was performed following the procedure listed in Scheme 4, Step6. White solid (45 g, 130.0 mmol, 86.7% yield). ESIMS found C₁₈H₂₄BFN₂O₃m/z 347.1 (M+1).

Preparation of 4-fluoro-substituted indazole intermediate (XXXIII) isdepicted below in Scheme 6.

Step 1

To a stirred solution of 3-fluoro-2-methylaniline (XXIX) (50 g, 399mmol, 1.0 eq) in CH₃CN (1.2 L) was added NBS (78 g, 439 mmol, 1.1 eq) inportions at 10° C., the resulting mixture was stirred at 25° C. for 1 h.LC/MS showed the reaction was completed. Saturated Na₂S₂O₃ (1.2 L) wasthen added slowly to the reaction mixture at 10° C., extracted withEtOAc (2 L) and the organic layer was concentrated under vacuum to givecrude product. The residue was washed with PE (1 L), the solid wasfiltered, washed again with PE (500 mL) and dried under vacuum to give4-bromo-3-fluoro-2-methylaniline (XXX) as a white solid (163.0 g, 798.9mmol, 66.7% yield). ESIMS found C₇H₇BrFN m/z 204.1 (M+1).

Step 2

To a stirred solution of 4-bromo-3-fluoro-2-methylaniline (XXX) (40 g,196 mmol, 1.0 eq) in HOAc (1.2 L) was added NaNO₂ (16 g, 235 mmol, 1.2eq) in portions at 10° C., the resulting mixture was stirred at 25° C.for 4 h. LC/MS showed the reaction was completed. Upon completion,aqueous NaOH (50%) was added to the reaction mixture until pH 7˜8, thenthe mixture was extracted with EtOAc (1.6 L), the organic layer wasdried over Na₂SO₄, filtered; filtrate was concentrated under vacuum togive crude 5-bromo-4-fluoro-1H-indazole (XXXI) (40 g, 186.0 mmol, 94.9%yield), which was used in step 3 without further purification. ¹H NMR(CDCl₃, 400 MHz) δ ppm 7.47-7.42 (m, 1H), 7.56-7.53 (m, 1H), 8.23 (s,1H); ESIMS found C₇H₄BrFN₂ m/z 215 (M+1).

Step 3

Preparation of 5-bromo-4-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole(XXXII) was performed following the procedure listed in Scheme 4, Step5. Brown oil (9.9 g, 33.1 mmol, 71.9% yield). ¹H NMR (CDCl₃, 400 MHz) δppm 1.75-1.67 (m, 3H), 2.10-1.76 (m, 2H), 2.52-2.14 (m, 1H), 3.76-3.71(m, 1H), 4.01-3.97 (m, 1H), 5.70-5.69 (m, 1H), 7.30-7.26 (m, 1H),7.47-7.45 (m, 1H), 8.06 (s, 1H); ESIMS found C₁₂H₁₂BrFN₂O m/z 299 (M+1).

Step 4

Preparation of4-fluoro-1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole(XXXIII) was performed following the procedure listed in Scheme 4, Step6. Red oil (25 g, 72.2 mmol, 72.2% yield). ¹H NMR (CD₃OD, 400 MHz) δ ppm1.72 (s, 12H), 2.12-1.74 (m, 5H), 2.52-2.16 (m, 1H), 3.85-3.80 (m, 1H),4.12-4.00 (m, 1H), 5.84-5.81 (m, 1H), 7.48 (d, J=8.0 Hz, 1H), 7.71-7.67(m, 1H), 8.15 (s, 1H); ESIMS found C₁₈H₂₄BFN₂O₃ m/z 347 (M+1).

Preparation of intermediate N-(5-bromopyridin-3-yl)pivalamide (XXXVI) isdepicted below in Scheme 7.

Step 1

To a solution of 3-amino-5-bromo pyridine (XXXIV) (1.0 g, 5.78 mmol) indry pyridine (10 mL) was added pivaloyl chloride (XXXV) (769 mg, 6.38mmol). The reaction mixture was stirred at room temperature for 3 h. Thereaction was poured into an ice water/saturated aqueous NaHCO₃ mixtureand stirred for 30 min. The precipitate was filtered, washed with coldwater and dried at room temperature to yieldN-(5-bromopyridin-3-yl)pivalamide (XXXVI) as an off-white solid (1.082g, 4.22 mmol, 73.1% yield). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 1.23 (s,9H), 8.37 (d, J=2 Hz, 1H), 8.39 (t, J=2 Hz, 1H), 8.80 (d, J=2 Hz, 1H),9.58 (brs, 1H); ESIMS found C₁₀H₁₃BrN₂O m/z 258.9 (Br⁸¹M+H).

The following intermediates were prepared in accordance with theprocedure described in the above Scheme 7.

N-(5-Bromopyridin-3-yl)isobutyramide (XXXVII): Off-white solid, (71%yield). ¹H NMR (CDCl₃) δ ppm 8.55-8.35 (m, 3H), 7.32 (s, 1H), 2.59-2.48(m, 1H), 1.28-1.27 (d, 6H); ESIMS found C₉H₁₁BrN₂O m/z 242.9 (Br⁷⁹M+H).

N-(5-Bromopyridin-3-yl)propionamide (XXXVIII): Off white solid (92%yield). ¹H NMR (DMSO-d₆) δ ppm 1.09 (t, J=7.54 Hz, 3H), 2.36 (q, J=7.54Hz, 2H), 8.36 (m, 2H), 8.65 (d, J=2.07 Hz, 1H), 10.26 (s, 1H); ESIMSfound C₈H₉BrN₂O m/z 231.1 (Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)butyramide (XXXIX): Yellow solid (2.1 g, 8.64mmol, 88.8% yield). ¹H NMR (CD₃OD, 400 MHz) δ ppm 1.02 (t, J=7.2 Hz,3H), 1.74 (sxt, J=7.2 Hz, 2H), 2.40 (t, J=7.2 Hz, 2H), 8.35 (d, J=2 Hz,1H), 8.46 (t, J=2 Hz, 1H), 8.63 (d, J=2 Hz, 1H); ESIMS found C₉H₁₁BrN₂Om/z 243.1 (Br⁷⁹M+H).

N-(5-Bromopyridin-3-yl)pentanamide (XL): Yellow solid (2.0 g, 7.78 mmol,85.3% yield). ¹H NMR (CD₃OD, 400 MHz) δ ppm 0.98 (t, J=7.4 Hz, 3H), 1.43(sxt, J=7.4 Hz, 2H), 1.70 (quin, J=7.4 Hz, 2H), 2.43 (t, J=7.6 Hz, 2H),8.35 (s, 1H), 8.45 (d, J=2 Hz, 1H), 8.64 (d, J=2 Hz, 1H); ESIMS foundC₁₀H₁₃BrN₂O m/z 256.9 (Br⁷⁹M+H).

N-(5-Bromopyridin-3-yl)-3-methylbutanamide (XLI): Off white solid, (67%yield), ¹H NMR (CDCl₃, 500 MHz) δ ppm 8.55-8.42 (m, 3H), 7.62 (s, 1H),2.31-2.18 (m, 3H), 1.02-1.01 (d, J=6 Hz, 6H); ESIMS found C₁₀H₁₃BrN₂Om/z 258.9 (Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)-3,3-dimethylbutanamide (XLII): Yellow solid (1.7g, 6.27 mmol, 78.6% yield). ¹H NMR (CD₃OD, 400 MHz) δ ppm 1.10 (s, 9H),2.29 (s, 2H), 8.36 (d, J=1.6 Hz, 1H), 8.46 (d, J=2.0 Hz, 1H), 8.64 (d,J=2.0 Hz, 1H); ESIMS found C₁₁H₁₅BrN₂O m/z 273.1 ((Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)-2-phenylacetamide (XLIII): White solid (2.5 g,8.59 mmol, 77.9% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm 3.76 (s, 2H),7.26-7.45 (m, 5H), 7.57 (brs, 1H), 8.33 (s, 1H), 8.37 (s, 2H); ESIMSfound C₁₃H₁₁BrN₂O m/z 292.8 (Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)benzamide (XLIV): White solid (2.7 g, 9.74 mmol,60% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm 7.40-7.52 (m, 2H), 7.52-7.62(m, 1H), 7.86 (d, J=7.2 Hz, 2H), 8.39 (d, J=1.6 Hz, 1H), 8.46 (s, 1H),8.55 (d, J=1.6 Hz, 1H), 8.57 (d, J=2.0 Hz, 1H); ESIMS found C₁₂H₉BrN₂Om/z 278.8 (Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)cyclopropanecarboxamide (XLV): Off-white solid,(83% yield), ¹H NMR (CDCl₃, 500 MHz) δ ppm 8.46-8.39 (m, 3H), 7.54 (bs,1H), 1.56-1.50 (m, 1H), 1.13-1.07 (m, 2H), 0.96-0.90 (m, 2H); ESIMSfound for C₉H₉BrN₂O m/z 240.9 (Br⁷⁹M+H).

N-(5-Bromopyridin-3-yl)cyclobutanecarboxamide (XLVI): Yellow solid (2.1g, 6.27 mmol, 86.6% yield). ¹H NMR (CD₃OD, 400 MHz) δ ppm 1.80-1.99 (m,1H), 1.99-2.15 (m, 1H), 2.16-2.30 (m, 2H), 2.30-2.45 (m, 2H), 3.25-3.35(m, 1H), 8.34 (d, J=2.0 Hz, 1H), 8.47 (s, 1H), 8.64 (d, J=2.0 Hz, 1H);ESIMS found C₁₀H₁₁BrN₂O m/z 257.1 (Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)cyclopentanecarboxamide (XLVII): Yellow solid(1.9 g, 7.06 mmol, 80.2% yield). ¹H NMR (CD₃OD, 400 MHz) δ ppm 1.57-1.74(m, 2H), 1.74-1.91 (m, 4H), 1.91-2.07 (m, 2H), 2.77-2.92 (m, 1H), 8.34(d, J=1.6 Hz, 1H), 8.45 (s, 1H), 8.65 (d, J=2.0 Hz, 1H); ESIMS foundC₁₁H₁₃BrN₂O m/z 271.1 (Br⁸¹M+H).

N-(5-bromopyridin-3-yl)cyclohexanecarboxamide (XLVIII): Yellow solid(2.0 g, 7.06 mmol, 84.3% yield). ¹H NMR (CD₃OD, 400 MHz) δ ppm 1.19-1.46(m, 3H), 1.46-1.63 (m, 2H), 1.74 (d, J=11.6 Hz, 1H), 1.88 (t, J=14.0 Hz,4H), 2.40 (tt, J=11.6 Hz, J=3.6 Hz, 1H), 8.34 (d, J=2.0 Hz, 1H), 8.44(t, J=2.0 Hz, 1H), 8.64 (d, J=2.0 Hz, 1H); ESIMS found C₁₂H₁₅BrN₂O m/z285.1 (Br⁸¹M+H).

N-(5-bromopyridin-3-yl)-2-cyclohexylacetamide (XLIX): Yellow solid (261mg, 0.878 mmol, 84.4% yield). ESIMS found C₁₃H₁₇BrN₂O m/z 297.1(Br⁸¹M+H).

Preparation of intermediate 5-bromo-N,N-dimethylpyridin-3-amine (LI) isdepicted below in Scheme 8.

Step 1

To a solution of 3,5-dibromopyridine (L) (2.37 g, 10.0 mmol) in dry DMF(20.0 mL) was added K₂CO₃ (4.5 g, 33 mmol) and dimethylaminohydrochloride (1.79 g, 22 mmol). The mixture was heated overnight at200° C. in a sealed tube. The solution was cooled to room temperatureand excess DMF was removed under vacuum. The residue was partitionedbetween EtOAc and water. The organic phase was separated. The aqueousphase was washed with EtOAc and the combined organic phases were driedover MgSO₄, and concentrated to afford5-bromo-N,N-dimethylpyridin-3-amine (LI) as an off-white solid (1.78 g,8.85 mmol, 88% yield). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 2.94 (s, 6H),7.25 (t, J=2 Hz, 1H), 7.91 (d, J=2 Hz, 1H), 8.07 (d, J=2 Hz, 1H); ESIMSfound C₇H₉BrN₂ m/z 201.1 (M+H).

Preparation of intermediate 5-bromo-N-isopropylpyridin-3-amine (LII) isdepicted below in Scheme 9.

Steps 1

To a solution of 5-bromopyridin-3-amine (XXXIV) (535 mg, 3.09 mmol) inMeOH (62 mL) was added acetone (296 μL, 4.02 mL). The pH was adjusted to4 using HOAc and stirred for 30 min. NaCNBH₃ (272 mg, 4.33 mmol) wasadded and stirred at room temperature overnight. The MeOH was removedunder vacuum and the residue was partitioned between EtOAc and saturatedaqueous NaHCO₃. The organic layer was dried over MgSO₄ and evaporatedunder vacuum. The crude product was purified on a silica gel column(100% hexane→90:10 hexane:EtOAc) to produce5-bromo-N-isopropylpyridin-3-amine (LII) as an oil which slowlysolidified into an off-white solid (309 mg, 1.44 mmol, 47% yield). ¹HNMR (DMSO-d₆, 500 MHz) δ ppm 1.12 (d, J=6.3 Hz, 6H), 3.55-3.59 (m, 1H),6.03 (d, J=7.9 Hz, 1H), 7.05-7.06 (m, 1H), 7.75 (d, J=2 Hz, 1H), 7.90(d, J=2 Hz, 1H); ESIMS found C₈H₁₁BrN₂ m/z 215.1 (M+H).

Preparation of intermediate1-(5-bromopyridin-3-yl)-N,N-dimethylmethanamine (LIV) is depicted belowin Scheme 10.

Steps 1

Preparation of 1-(5-bromopyridin-3-yl)-N,N-dimethylmethanamine (LIV) wasperformed following the procedure listed in Scheme 9, Step 1. Brown oil(1.20 g, 5.59 mmol, 45% yield). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 2.15 (s,6H), 3.43 (s, 2H), 7.94 (s, 1H), 8.47 (d, J=1.1 Hz, 1H), 8.59 (d, J=2.2Hz, 1H); ESIMS found C₈H₁₁BrN₂ m/z 215 (M^(Br79)+H) and 217(M^(Br81)+H).

Preparation of intermediate3-bromo-5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridine (LV) is depictedbelow in Scheme 11.

Steps 1

To a mixture of 5-bromopyridine-3-carbaldehyde (LIII) (6.00 g, 32.26mmol, 1.0 eq), 3,3-difluoropyrrolidine (5.56 g, 38.71 mmol, 1.20 eq) andTEA (5.39 mL, 38.71 mmol, 1.2 Eq) in DCE (200 mL) was stirred at roomtemperature for 30 min, then added sodium triacetoxyborohydride (10.25g, 48.38 mmol, 1.50 eq) in one portion at room temperature under N₂. Themixture was stirred at room temperature for 6 hours. TLC showed thereaction was complete. The reaction was quenched with 1N NaOH (100 mL),extracted with DCE (100 mL×2). The combined organic layers were washedwith brine (100 mL), dried and concentrated. The residue was purified bysilica gel chromatography (column height: 50 mm, diameter: 50 mm,300-400 mesh silica gel, DCM/MeOH=30/1→20/1) to give3-bromo-5-((3,3-difluoropyrrolidin-1-yl)methyl) pyridine (LV): Yellowoil (8.00 g, 28.9 mmol, 89.5% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm 2.30(spt, J=7.2 Hz. 2H), 2.75 (t, J=6.8 Hz, 2H), 2.91 (t, J=13.2 Hz, 2H),7.85 (s, 1H), 8.45 (s, 1H), 8.59 (d, J=2 Hz, 1H); ESIMS found forC₁₀H₁₁BrF₂N₂ m/z 277.0 (M+H).

The following intermediates were prepared in accordance with theprocedure described in the above Scheme 10 or Scheme 11.

3-Bromo-5-(pyrrolidin-1-ylmethyl)pyridine (LVI): Golden liquid (1.35 g,97% yield). ¹H NMR (DMSO-d₆) 1.68-1.71 (m, 4H), 2.42-2.44 (m, 4H), 3.60(s, 2H), 7.96 (s, 1H), 8.48 (d, J=2 Hz, 1H), 8.58 (d, J=3 Hz, 1H); ESIMSfound for C₁₀H₁₃BrN₂ m/z 242.2 (M+H).

3-Bromo-5-(piperidin-1-ylmethyl)pyridine (LVII): Brown liquid (13.1 g,94% yield). ¹H NMR (DMSO-d₆) 1.36-1.39 (m, 2H), 1.46-1.51 (m, 4H),2.31-2.32 (m, 4H), 3.46 (s, 2H), 7.94 (s, 1H), 8.47 (d, J=2 Hz, 1H),8.58 (d, J=3 Hz, 1H); ESIMS found for C₁₁H₁₅BrN₂ m/z 257.0 (M+H).

N-((5-Bromopyridin-3-yl)methyl)ethanamine (LVIII): Golden liquid (1.29g, 6.00 mmol, 60% yield). ¹HNMR (CDCl₃, 400 MHz) δ ppm 1.14 (t, J=7.2Hz, 3H), 2.67 (q, J=7.2 Hz, 2H), 3.79 (s, 2H), 7.85 (t, J=2 Hz, 1H),8.46 (d, J=1.6 Hz, 1H), 8.56 (d, J=2.4 Hz, 1H); ESIMS found forC₈H₁₁BrN₂ m/z 215.1 (M+H).

N-Benzyl-1-(5-bromopyridin-3-yl)methanamine (LIX): Yellow oil (8.0 g,28.9 mmol, 89.5% yield). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 3.71 (s, 2H),3.74 (s, 2H), 7.18-7.28 (m, 1H), 7.28-7.40 (m, 4H), 8.04 (s, 1H), 8.52(s, 1H), 8.58 (s, 1H); ESIMS found for C₁₃H₁₃BrN₂ m/z 277.1 (M+H).

Preparation of intermediate tert-butyl (5-bromopyridin-3-yl)methyl(cyclopentylmethyl)carbamate (LXIV) is depicted below in Scheme 12.

Step 1

To a solution of 5-bromonicotinaldehyde (LIII) (2.0 g, 10.8 mmol, 1 eq)in MeOH (20 mL) was added NaBH₄ (2.4 g, 64.9 mmol, 6 eq) and thereaction mixture was stirred at room temperature for 3 h. The mixturewas concentrated in vacuo and the residue was diluted in water (15 mL),the aqueous phase was extracted with DCM (10 mL×3). The combined organiclayers were dried over MgSO₄, filtered and concentrated in vacuo toafford (5-bromopyridin-3-yl)methanol (LX) (1.8 g, 9.57 mmol, 90.0%yield) as a colorless oil. ¹H NMR (CDC₃, 500 MHz) δ ppm 4.73 (s, 2H),7.90 (s, 1H), 8.47 (s, 1H), 8.57 (s, 1H). ESIMS found for C₆H₆BrNO m/z188.0 (M+H).

Step 2

To a stirred solution of (5-bromopyridin-3-yl)methanol (LX) (1.60 g, 8.5mmol, 1 eq), phthalimide (1.24 g, 8.5 mmol, 1 eq) and PPh₃ (3.33 g,12.75 mmol, 1.5 eq) in anhydrous THF (15 mL) was added DEAD (2.21 g,12.75 mmol, 1.5 eq) dropwise at 0° C. under N₂. Then the reactionmixture was stirred at room temperature for 6 h. The mixture was washedwith saturated NaHCO₃ solution (15 mL), water (15 mL) and brine (15 mL)subsequently. The organic layers were dried over MgSO₄, concentratedunder reduced pressure, the resultant residue was purified by flashchromatography on silica gel (PE:EtOAc=4:1) to give2-((5-bromopyridin-3-yl)methyl)isoindoline-1,3-dione (LXI) (2.5 g, 7.88mmol, 82.3% yield) as a white solid. ESIMS found for C₁₄H₉BrN₂O₂ m/z317.1 (M+H).

Step 3

A solution of 2-((5-bromopyridin-3-yl)methyl)isoindoline-1,3-dione (LXI)(1.9 g, 6.0 mmol, 1 eq) and hydrazine hydrate (2.0 g, 40 mmol, 6 eq) inEtOH (20 mL) was heated at 70° C. for 3 h. The mixture was filteredthrough a Celite® pad and the filtrate was concentrated in vacuo, thecrude product was dissolved in 1N HCl solution (15 mL) and concentratedto dryness, then it was washed with acetone (10 mL×3), the precipitatewas collected by filtration, dried in vacuo to give(5-bromopyridin-3-yl)methanamine (LXII) (1.3 g, 6.95 mmol, 97.7% yield)as a white solid. ¹H NMR (D₂O, 500 MHz) δ ppm 4.34 (s, 2H), 8.56 (s,1H), 8.75 (d, J=1.2 Hz, 1H), 8.91 (d, J=1.6 Hz, 1H). ESIMS found forC₆H₇BrN₂ m/z 187.0 (M+H).

Step 4

A solution of (5-bromopyridin-3-yl)methanamine (LXII) (1.30 g, 5.8 mmol,1.0 eq), cyclopentanecarbaldehyde (0.57 g, 5.8 mmol, 1.0 eq) and TEA(0.60 g, 5.8 mmol, 1.0 eq) in MeOH (15 mL) was stirred at roomtemperature for 2 h. Then NaBH₃CN (1.98 g, 34.6 mmol, 6.0 eq) was addedand the mixture was stirred at the same temperature for another 3 h. Thesolvent was removed under reduced pressure and the residue was dilutedin water (20 mL) and extracted with DCM (10 mL×3), combined organiclayers were dried over MgSO₄ and concentrated in vacuo to give1-(5-bromopyridin-3-yl)-N-(cyclopentylmethyl)methanamine (LXIII) (1.23g, 4.57 mmol, 79.3% yield) as a yellow oil. ¹H NMR (CDCl₃, 400 MHz) δppm 1.07-1.23 (m, 2H), 1.47-1.67 (m, 4H), 1.70-1.84 (m, 2H), 2.02 (spt,J=7.6 Hz. 1H), 2.53 (d, J=7.2 Hz, 2H), 3.80 (s, 2H), 7.86 (s, 1H), 8.47(s, 1H), 8.56 (d, J=2.0 Hz, 1H); ESIMS found for C₁₂H₁₇BrN₂ m/z 269.1(M+H).

Step 5

To a solution of 1-(5-bromopyridin-3-yl)-N-(cyclopentylmethyl)methanamine (LXIII) (1.00 g, 3.7 mmol, 1 eq) and TEA (0.93 g, 9.2 mmol,2.5 eq) in DCM (20 mL) was added portionwise (Boc)₂O (0.85 g, 4.0 mmol,1.1 eq) at 0° C., the reaction mixture was stirred at room temperaturefor 1 h. The mixture was washed with water (10 mL), brine (10 mL), theorganic layer was separated, dried over MgSO₄ and concentrated in vacuoto give tert-butyl (5-bromopyridin-3-yl)methyl(cyclopentylmethyl)carbamate (LXIV) (1.25 g, 3.38 mmol, 91.9% yield) asa white solid. ESIMS found for C₁₇H₂₅BrN₂O₂ m/z 369.1 (M+H).

Preparation of intermediate 3-bromo-5-(cyclohexyloxy)pyridine (LXVII) isdepicted below in Scheme 13.

Step 1

To a solution of 5-bromopyridin-3-ol (LXV) (523 mg, 3.01 mmol) in THF(30 mL) cooled to 0° C. were added triphenylphosphine (867 mg, 3.31mmol) and cyclohexanol (LXVI) (331 mg, 3.31 mmol) followed by(E)-bis(4-chlorobenzyl) diazene-1,2-dicarboxylate (1.21 g, 3.31 mmol),added portionwise. The reaction mixture was then stirred at 25° C.overnight. The reaction was worked-up with a EtOAc-NaHCO₃ extraction andthe solid filtered off. The solvent was removed and the residue waspurified by Isco (20% EtOAc-Hexanes) to give3-bromo-5-(cyclohexyloxy)pyridine (LXVII) (209 mg, 0.82 mmol, 27.2%yield) as a yellow oil. ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 1.21-1.31 (m,1H) 1.34-1.48 (m, 4H) 1.49-1.57 (m, 1H) 1.70 (br dd, J=9.74, 4.25 Hz,2H) 1.88-1.96 (m, 2H) 2.50 (dt, J=3.70, 1.72 Hz, 5H) 4.46-4.54 (m, 1H)7.72 (t, J=2.20 Hz, 1H) 8.24 (d, J=1.92 Hz, 1H) 8.27 (d, J=2.47 Hz, 1H).

The following intermediate was prepared in accordance with the proceduredescribed in the above Scheme 13.

tert-Butyl 4-((5-bromopyridin-3-yl)oxy)piperidine-1-carboxylate(LXVIII): Yellow oil (244 mg, 0.683 mmol, 23.2% yield). ESIMS found forC₁₅H₂₁BrN₂O₃ m/z 358.3 (M+H).

Preparation of intermediate 3-(benzyloxy)-5-bromopyridine (LXX) isdepicted below in Scheme 14.

Step 1

To a solution of 5-bromopyridin-3-ol (LXV) (174 mg, 1.0 mmol) in DMF (3mL) was added potassium carbonate (415 mg, 3.0 mmol). The slurry washeated at 90° C. for 1 hour and then cooled to 25° C. The(bromomethyl)benzene (LXIX) (171 mg, 1.0 mmol) was added and the mixturewas stirred at 25° C. overnight. The reaction was worked-up using asaturated sodium bicarbonate and ethyl acetate extraction. The productwas purified by ISCO column eluted with 40-100% EtOAc-Hexanes. The3-(benzyloxy)-5-bromopyridine (LXX) (105 mg, 0.398 mmol, 39.8% yield)was obtained as yellow oil. MS: 266.1. ESIMS found for C₁₂H₁₀BrNO m/z266.1 (M+H).

The following intermediates were prepared in accordance with theprocedure described in the above Scheme 14.

3-Bomo-5-(2-(pyrrolidin-1-yl)ethoxy)pyridine (LXXI): Yellow oil ((97 mg,0.358 mmol, 15.56% yield). ESIMS found for C₁₁H₁₅BrN₂O m/z 272.2 (M+H).

2-((5-bromopyridin-3-yl)oxy)-N,N-dimethylethan-1-amine (LXXII): Yellowoil (97 mg, 0.396 mmol, 28.9% yield). ESIMS found for C₉H₁₃BrN₂O m/z245.1 (M+H).

1-(2-(3-bromo-5-fluorophenoxy)ethyl)pyrrolidine (LXXIII): Yellow oil(370 mg, 1.284 mmol, 85.8% yield). ESIMS found for C₁₂H₁₅BrFNO m/z 289.0(M+H).

2-(3-bromo-5-fluorophenoxy)-N,N-dimethylethan-1-amine (LXXIV): Yellowoil (364 mg, 1.389 mmol, 50.2% yield). ESIMS found for C₁₀H₁₃BrFNO m/z263.9 (M+H).

Preparation of intermediate tert-butyl4-(2-((5-bromopyridin-3-yl)amino)-2-oxoethyl)piperidine-1-carboxylate(LXXVI) is depicted below in Scheme 15.

Step 1

To a solution of 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)acetic acid(LXXV) (3.4 g, 13.97 mmol) in DCM (10 mL) was added DMF (1 mL). Thesolution was cooled in ice-water to 0° C. Oxalyl chloride (1.835 mL,20.96 mmol) was then added dropwise. The mixture was stirred for onehour at 25° C. The organic volatile was then removed under vacuum. Theresidue was dissolved in DCM (10 mL). DMAP (0.171 g, 1.397 mmol) and5-bromopyridin-3-amine (XXXIV) (2.418 g, 13.97 mmol) were added to thesolution and cooled to 0° C. DIEA (4.88 ml, 27.9 mmol) was then addeddropwise and the mixture was stirred for 2 hours at 25° C. The reactionwas worked-up with DCM and saturated NaHCO3. The product was purified byISCO eluted with 0-100% EtOAc-Hexanes. The tert-butyl4-(2-((5-bromopyridin-3-yl)amino)-2-oxoethyl)piperidine-1-carboxylate(LXXVI) (2.82 g, 7.08 mmol, 50.7% yield) was obtained as yellow oil.ESIMS found for C₁₇H₂₄BrN₃O₃ m/z 343.1 (M-56).

The following intermediate was prepared in accordance with the proceduredescribed in the above Scheme 15.

N-(5-Bromopyridin-3-yl)-2-(dimethylamino)acetamide (LXXVII): Yellow oil(528 mg, 2.05 mmol, 19.0% yield). ESIMS found for C₉H₁₂BrN₃O m/z 259.3(M+H).

Preparation of tert-butyl(1-(6-chloropyrazin-2-yl)azetidin-3-yl)carbamate (LXXX) is depictedbelow in Scheme 16.

Step 1

To a solution of tert-butyl azetidin-3-ylcarbamate hydrochloride(LXXVIII) (2 g, 9.58 mmol) in dry DMF (19.2 mL) was added DIPEA (8.37ml, 47.9 mmol). To this mixture was added 2,6-dichloropyrazine (LXXIX)(1.428 g, 9.58 mmol) and the reaction was stirred at 95° C. for 3 hours.The reaction was quenched with water (20 mL) and extracted with EtOAc.The organic layer was dried over anhydrous Na₂SO₄, filtered andconcentrated. The residue was purified by silica gel columnchromatography (40 g) (100% hexanes→hexanes:EtOAc 1:1) to yieldtert-butyl (1-(6-chloropyrazin-2-yl)azetidin-3-yl)carbamate (LXXX)(2.2882 g, 8.04 mmol, 84% yield) as a white solid. ESIMS found forC₁₂H₁₇ClN₄O₂ m/z 285.1 (M+H).

Preparation of intermediate 4-(2-fluorophenyl)-3-nitropyridin-2-amine(LXXXIV) is depicted below in Scheme 17.

Step 1

A solution of 4-bromo-3-nitropyridin-2-amine (LXXXI) (5.00 g, 22.9 mmol,1.00 eq), (2-fluorophenyl)boronic acid (LXXXII) (3.82 g, 27.5 mmol, 1.20eq), Pd(PPh₃)₄ (1.32 g, 1.14 mmol, 0.05 eq), and Na₂CO₃ (4.85 g, 45.8mmol, 2 eq) in a mixture of toluene (25 mL), H₂O (9 mL) and EtOH (6 mL)was stirred at 75° C. for 15 h under nitrogen atmosphere. The reactionmixture was the washed with brine (50 mL) and dried over anhydrousNa₂SO₄, filtered and concentrated in vacuo. The resultant residue waspurified by chromatography on silica gel (PE:EtOAc=3:1) to give4-(2-fluorophenyl)-3-nitropyridin-2-amine (LXXXIII) (4.0 g, 17.15 mmol,74.9%) as a yellow solid. ¹H NMR (CDCl₃, 400 MHz) δ ppm 6.29 (brs, 2H),6.68 (d, J=4.8 Hz, 1H), 7.14 (t, J=5.2 Hz, 1H), 7.23-7.50 (m, 3H), 8.32(d, J=4.8 Hz, 1H); ESIMS found C₁₁H₈FN₃O₂ m/z 234.2 (M+H).

Step 2

A mixture of 4-(2-fluorophenyl)-3-nitropyridin-2-amine (LXXXIII) (2.8 g,12.0 mmol, 1 eq) and Pd/C (0.2 g) in MeOH (200 mL) was stirred under 50psi of H₂ at room temperature overnight. The reaction was monitored byTLC. The mixture was filtered and the filtrate was concentrated in vacuoto produce 4-(2-fluorophenyl)pyridine-2,3-diamine (LXXXIV) (1.55 g, 7.63mmol, 63.6% yield) as a black solid. ¹H NMR (CDCl₃, 400 MHz) δ ppm 3.38(brs, 2H), 4.40 (brs, 2H), 6.64 (d, J=4.8 Hz, 1H), 7.11-7.53 (m, 4H),7.72 (d, J=4.8 Hz, 1H); ESIMS found C₁₁H₁₀FN₃ m/z 204.2 (M+H).

The following intermediates were prepared in accordance with theprocedure described in the above Scheme 17.

4-(3-Fluorophenyl)pyridine-2,3-diamine (LXXXV): Grey solid, (1.55 g,7.63 mmol, 86.0% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm 3.50 (brs, 2H),4.36 (brs, 2H), 6.63 (d, J=3.6 Hz, 1H), 7.3-7.37 (m, 3H), 7.47 (d, J=6Hz, 1H), 7.72 (d, J=3.6 Hz, 1H); ESIMS found C₁₁H₁₀FN₃ m/z 204.2 (M+H).

4-(4-Fluorophenyl)pyridine-2,3-diamine (LXXXVI): Grey solid, (1.55 g,7.63 mmol, 60.0% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm 3.46 (brs, 2H),4.36 (brs, 2H), 6.62 (s, 1H), 7.19 (s, 2H), 7.43 (s, 2H), 7.70 (d, J=3.2Hz, 1H); ESIMS found C₁₁H₁₀FN₃ m/z 204.1 (M+H).

4-(4-Fluorophenyl)pyridine-2,3-diamine (LXXXVII): Grey solid, (1.55 g,7.63 mmol, 60.0% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm 3.46 (brs, 2H),4.36 (brs, 2H), 6.62 (s, 1H), 7.19 (s, 2H), 7.43 (s, 2H), 7.70 (d, J=3.2Hz, 1H); ESIMS found C₁₁H₁₁₀FN₃ m/z 204.1 (M+H).

4-(Thiophen-3-yl)pyridine-2,3-diamine (LXXXVIII): Yellow solid, (1.9 g,9.94 mmol, 84.9% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm 3.80 (brs, 2H),4.34 (brs, 2H), 6.77 (s, 1H), 7.18 (s, 1H), 7.27 (s, 2H), 7.44 (s, 1H),7.68 (s, 1H); ESIMS found C₉H₉N₃S m/z 192.2 (M+H).

4-(Furan-3-yl)pyridine-2,3-diamine (LXXXIX): Black solid, (1.9 g, 10.84mmol, 89.0% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm 3.64 (brs, 2H), 4.32(brs, 2H), 6.65 (s, 1H), 6.69 (d, J=4.8 Hz, 1H), 7.58 (s, 1H), 7.67 (d,J=4.8 Hz, 1H), 7.71 (s, 1H); ESIMS found C₉H₉N₃O m/z 176.3 (M+H).

4-(Thiophen-2-yl)pyridine-2,3-diamine (XC): Yellow solid, (0.90 g, 4.71mmol, 96.5% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm 3.63 (brs, 2H), 4.35(brs, 2H), 6.71 (s, 1H), 7.27 (s, 1H), 7.45 (s, 1H), 7.49 (s, 1H), 7.69(s, 1H); ESIMS found C₉H₉N₃S m/z 192.1 (M+H).

3-(2,3-Diaminopyridin-4-yl)-5-fluorophenol (XCI): White solid (303 mg,1.38 mmol, 84.4% yield). ESIMS found for C₁₁H₁₀FN₃O m/z 220.1 (M+H).

4-(3-Fluoro-5-methoxyphenyl)pyridine-2,3-diamine (XCII): White solid(404 mg, 1.73 mmol, 75.1% yield). ESIMS found for C₁₂H₁₂FN₃O m/z 234.1(M+H).

4-(3-Fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)pyridine-2,3-diamine(XCIII): Black oil (368 mg, 1.163 mmol, 95.0% yield). ESIMS found forC₁₇H₂₁FN₄O m/z 317.1 (M+H).

4-(3-(2-(Dimethylamino)ethoxy)-5-fluorophenyl)pyridine-2,3-diamine(XCIV): Black oil (352 mg, 1.212 mmol, 83.6% yield). ESIMS found forC₁₅H₁₉FN₄O m/z 291.1 (M+H).

Preparation of intermediate 3-nitro-[4,4′-bipyridin]-2-amine (XCVIII) isdepicted below in Scheme 18.

Step 1

To a solution of 4-chloro-3-nitropyridin-2-amine (XCV) (5.00 g, 28.9mmol, 1.00 eq) and4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (XCVI) (7.1 g,34.6 mmol, 1.20 eq) in a mixture of toluene (30 mL), H₂O (18 mL) andEtOH (6 mL) was added Pd(PPh₃)₄ (1.0 g, 0.87 mmol, 0.03 eq) and Na₂CO₃(6.1 g, 57.6 mmol, 2 eq). The mixture was stirred at 75° C. for 15 hunder a nitrogen atmosphere. The reaction mixture was then poured intobrine (100 mL) and extracted with EtOAc (30 mL×3), the combined organiclayers were dried over anhydrous Na₂SO₄, filtered and concentrated invacuo. The resultant residue was purified by chromatography on silicagel (PE:EtOAc=5:1→1:1) to afford 3-nitro-[4,4′-bipyridin]-2-amine(XCVII) (1.80 g, 8.33 mmol, 28.8% yield) as a yellow solid. ESIMS foundC₁₀H₈N₄O₂ m/z 217.1 (M+H).

Step 2

To a solution of 3-nitro-[4,4′-bipyridin]-2-amine (XCVII) (1.80 g, 8.33mol, 1 eq) in MeOH (50 mL) was added Pd/C (0.5 g) under a nitrogenatmosphere. The mixture was stirred under 50 psi of H₂ for 6 h at roomtemperature. Then the mixture was filtered through a Celite pad and thefiltrate was concentrated in vacuo to afford[4,4′-bipyridine]-2,3-diamine (XCVIII) (1.4 g, 7.52 mmol, 90.4% yield)as a black solid. ESIMS found C₁₀H₁₀N₄ m/z 186.0 (M+H).

Preparation of intermediate 3-nitro-[4,4′-bipyridin]-2-amine (CI) isdepicted below in Scheme 19.

Step 1

A solution of 4-chloro-3-nitropyridin-2-amine (XCV) (5.00 g, 28.9 mmol,1.00 eq), 2-(tributylstannyl)pyridine (XCIX) (15.9 g, 43.4 mmol, 1.50eq), and Pd(PPh₃)₂Cl₂ (1.05 g, 1.44 mmol, 0.05 eq) in a mixture oftoluene (25 mL) and H₂O (9 mL) was stirred at 75° C. for 16 h under anitrogen atmosphere. The reaction mixture was then poured into brine (80mL) and extracted with EtOAc (30 mL×3). The combined organic layers weredried over anhydrous Na₂SO₄, filtered and concentrated in vacuo. Theresultant residue was purified by chromatography on silica gel(PE:EtOAc=5:1→1:1) to afford 3′-nitro-[2,4′-bipyridin]-2′-amine (C) (1.6g, 7.40 mmol, 25.6% yield) as a yellow solid. ESIMS found C₁₀H₈N₄O₂ m/z217.1 (M+H).

Step 2

To a solution of compound 3′-nitro-[2,4′-bipyridin]-2′-amine (C) (1.6 g,7.4 mmol, 1.0 eq) in MeOH (50 mL) was added Pd/C (0.5 g) under anitrogen atmosphere. The mixture was stirred under 50 psi of H₂ for 6 hat room temperature. The mixture was then filtered and concentrated invacuo to afford [2,4′-bipyridine]-2′,3′-diamine (CI) (1.1 g, 5.91 mmol,79.8%) as a black solid. ESIMS found C₁₀H₁₀N₄ m/z 186.1 (M+H).

Preparation of intermediate4-(4-methylpiperazin-1-yl)pyridine-2,3-diamine (CIII) is depicted belowin Scheme 20.

Step 1

A solution of 4-bromo-3-nitropyridin-2-amine (LXXXI) (2.50 g, 11.47mmol) in 1-methylpiperazine (4 mL, 34.5 mmol) was heated at 140° C.overnight. The reaction was poured into an EtOAc/H₂O mixture; theorganic layer was separated, dried over MgSO₄ and concentrated undervacuum. The crude product was purified on a silica gel column (100%CHCl₃→3:97 MeOH(7N NH₃):CHCl₃) to give4-(4-methylpiperazin-1-yl)-3-nitropyridin-2-amine (CII) as a yellowsolid (1.80 g, 7.59 mmol, 66.1% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm2.36 (s, 3H), 2.54 (t, J=4.8 Hz, 4H), 3.25 (t, J=5 Hz, 4H), 6.18 (s,2H), 6.22 (d, J=6 Hz, 1H), 7.85 (d, J=6 Hz, 1H); ESIMS found C₁₀H₂₅N₅O₂m/z 238.0 (M+H).

Step 2

To a solution of 4-(4-methylpiperazin-1-yl)-3-nitropyridin-2-amine (CII)(1.80 g, 7.59 mmol) in MeOH (52 mL) was added 10% Pd/C (0.5 g). Thesolution was purged with hydrogen and stirred at room temperature underhydrogen for 4 h. The suspension was filtered through Celite® and theconcentrated under vacuum to produce4-(4-methylpiperazin-1-yl)pyridine-2,3-diamine (CIII) as black solid(1.4 g, 6.75 mmol, 89.0% yield). ¹H NMR (CDCl₃, 400 MHz): δ ppm 2.38 (s,3H), 2.60 (brs, 4H), 2.99 (s, 4H), 3.49 (brs, 2H), 4.12 (brs, 2H), 6.52(d, J=5.6 Hz, 1H), 7.64 (d, J=5.6 Hz, 1H); ESIMS found C₁₀H₁₇N₅ m/z208.1 (M+H).

The following intermediate was prepared in accordance with the proceduredescribed in the above Scheme 20.

4-(Piperidin-1-yl)pyridine-2,3-diamine (CIV): Black solid, (2.40 g,12.48 mmol, 92.5% yield). ¹HNMR (CDCl₃, 400 MHz): δ ppm 1.61 (brs, 2H),1.73 (s, 4H), 2.88 (s, 4H), 3.48 (brs, 2H), 4.13 (brs, 2H), 6.50 (d,J=5.2 Hz, 1H), 7.63 (d, J=4.8 Hz, 1H); ESIMS found C₁₀H₁₆N₄ m/z 193.1(M+H).

Preparation of intermediate 4-(2-fluorophenyl)-3-nitropyridin-2-amine(CVII) is depicted below in Scheme 21.

Step 1

4-Chloro-3-nitro-pyridin-2-amine (XCV) (3.00 g, 17.3 mmol, 1.0 eq) and4-methyl-1H-imidazole (CV) (2.84 g, 34.6 mmol, 2.0 eq) were taken upinto a microwave tube in DMF (20 mL). The sealed tube was heated at 130°C. for 30 min under microwave. TLC showed the starting material wasconsumed, LC/MS showed the desired product was found. 10% NH₄Cl (60 mL)were added. The aqueous layer was extracted with DCM (2×100 mL). Thecombined organic layers were washed with brine (100 mL), dried overNa₂SO₄, concentrated in vacuum. The residue was purified bychromatography on silica gel (PE:THF=1:1) to give the product4-(4-methylimidazol-1-yl)-3-nitro-pyridin-2-amine (CVI) (1.20 g, 5.47mmol, 31.6% yield) as a yellow solid. ¹H NMR (CDCl₃, 400 MHz) δ ppm 2.30(d, J=0.75 Hz, 3H), 5.96-6.26 (m, 2H), 6.68 (d, J=5.02 Hz, 1H),6.72-6.75 (m, 1H), 7.57 (d, J=1.0 Hz, 1H), 8.32 (d, J=5.14 Hz, 1H);ESIMS found C₉H₉N₅O₂ m/z 219.1 (M+H).

Step 2

To a solution of 4-(4-methylimidazol-1-yl)-3-nitro-pyridin-2-amine (CVI)(900.0 mg, 4.11 mmol, 1.0 eq) in MeOH (50 mL) was added Pd/C (100.0 mg,4.11 mmol, 1.0 eq) at room temperature. The mixture was stirred at 20°C. under H₂ for 2 hr. TLC (DCM:MeOH=20:1) showed that starting thematerial was consumed completely. The mixture was filtered andconcentrated to afford 4-(4-methyl-1H-imidazol-1-yl)pyridine-2,3-diamine(CVII) (750.0 mg, 3.96 mmol, 96.4% yield) as a brown solid. ¹H NMR(CDCl₃, 400 MHz) δ ppm 2.17 (s, 3H), 4.58 (brs, 2H), 5.85 (brs, 2H),6.36 (d, J=5.4 Hz, 1H), 7.06 (s, 1H), 7.34 (s, 1H), 7.34 (s, 1H), 7.69(d, J=0.88 Hz, 1H); ESIMS found C₉H₁₁N₅ m/z 190.1 (M+H).

Preparation of intermediate4-(5-fluorothiophen-2-yl)pyridine-2,3-diamine (CX) is depicted below inScheme 22.

Step 1

A solution of 2-chloro-3-nitro-pyridin-4-amine (XCV) (1.5 g, 8.64 mmol),2-(5-fluorothiophen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane(CVIII) (2.96 g, 12.96 mmol), Pd(dppf)Cl₂ (632 mg, 0.86 mmol) and Cs₂CO₃(5.63 g, 17.29 mmol) in dioxane (30 mL) and H₂O (5 mL) was de-gassed andthen heated to 100° C. under N² for 3 h. TLC (PE:EtOAc=1:1) showed thestarting material was consumed completely. The mixture was concentratedin vacuum to give a residue, which was purified by column chromatographyto afford 4-(5-fluorothiophen-2-yl)-3-nitropyridin-2-amine (CIX) (800mg, 3.34 mmol, 38.7% yield). ESIMS found C₉H₆FN₃O₂S m/z 240.1 (M+H).

Step 2

A solution of 4-(5-fluorothiophen-2-yl)-3-nitropyridin-2-amine (CIX)(700 mg, 2.93 mmol), Fe (817 mg, 14.63 mmol) and NH₄Cl (939 mg, 17.56mmol) in EtOH (18 mL) and H₂O (6 mL) was heated to 80° C. for 2 h. TLC(PE:EtOAc=1:1) showed the starting material was consumed completely. Themixture was filtered, washed with HCl/EtOH, concentrated, basified topH=7˜8, extracted with EtOAc and H₂O, the organic layer was concentratedto give 4-(5-fluorothiophen-2-yl)pyridine-2,3-diamine (CX) (550 mg, 2.63mmol, 89.7% yield). ESIMS found C₉H₈FN₃S m/z 210.0 (M+H).

The following intermediates were prepared in accordance with theprocedure described in the above Scheme 22.

4-(5-Methylthiophen-2-yl)pyridine-2,3-diamine (CXI): Brown solid, (1.20g, 5.85 mmol, 86.0% yield). ¹H NMR (CD₃OD, 400 MHz) δ ppm 2.54 (s, 3H),6.63 (d, J=4.8 Hz, 1H), 6.85 (s, 1H), 7.12 (s, 1H), 7.38 (d, J=5.2 Hz,1H); ESIMS found C₁₀H₁₁N₃S m/z 206.2 (M+H).

1-(5-(2,3-Diaminopyridin-4-yl)thiophen-2-yl)ethan-1-one (CXII): Brownsolid, (500 mg, 2.14 mmol, 56.4% yield). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm2.55 (s, 3H), 4.89 (brs, 2H), 5.80 (brs, 2H), 6.52 (d, J=5.2 Hz, 1H),7.33 (d, J=5.2 Hz, 1H), 7.46 (d, J=4.0 Hz, 1H), 7.96 (d, J=4.0 Hz, 1H);ESIMS found C₁₁H₁₁N₃OS m/z 234 (M+H).

Preparation of intermediate4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)pyridine-2,3-diamine(CXVII) is depicted below in Scheme 23.

Step 1

A solution of 3-bromo-5-fluorobenzaldehyde (CXIII) (20.0 g, 98.2 mmol,1.0 eq) in MeOH (1.8 L) was added N¹,N¹-dimethylethane-1,2-diamine (21.5mL, 196.4 mmol, 2.0 eq). The pH was adjusted to 6 using HOAc and stirredfor 1 h. NaCNBH₃ (8.6 g, 137.5 mmol, 1.4 eq) was added and stirred atroom temperature overnight. The MeOH was removed under vacuum and theresidue was partitioned between CHCl₃ and saturated aqueous NaHCO₃. Theorganic layer was dried over MgSO₄ and evaporated under vacuum. Thecrude product was purified on a silica gel column (100% CHCl₃→3:97MeOH[7N NH₃]:CHCl₃) to produceN¹-(3-bromo-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine (CXIV) as ayellow oil (13.0 g, 49.9 mmol, 51% yield). ESIMS found C₁₀H₁₄BrFN₂ m/z261.0 (M+H).

Step 2

A solution ofN¹-(3-bromo-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine (CXIV)(13.0 g, 49.9 mmol, 1.0 eq), bis(pinacolato)diboron (12.6 g, 59.9 mmol,1.2 eq), KOAc (12.1 g, 124.3 mmol, 2.5 eq) and dioxane (600 mL) waspurged with argon. Pd(dppf)Cl₂ (2.0 g, 2.47 mmol, 0.05 eq) was added tothe reaction and purged again with argon. The solution was heated at 90°C. for 2 h. Once TLC showed the disappearance of (CXIV), the solutionwas cooled to room temperature and then concentrated under reducedpressure to produce crudeN¹-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(CXV) (7.4 g, 24.0 mmol, 48.2% yield).

Step 3

To a solution ofN¹-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(CXV) (5.0 g, 16.22 mmol, 1.2 eq) in water (25 mL) was added K₂CO₃ (448mg, 3.24 mmol, 2.0 eq), 4-bromo-3-nitropyridin-2-amine (LXXXI) (3.5 g,16.22 mmol, 1.0 eq) and Pd(dppf)Cl₂ (1.0 g, 81.0 μmol, 0.05 eq). Thesolution was purged with argon and heated at 100° C. for 48 h. Thesolution was cooled to room temperature and then concentrated underreduced pressure. The residue was purified on a silica gel column (100%CHCl₃→2:98 MeOH[7N NH₃]:CHCl₃) to giveN¹-(3-(2-amino-3-nitropyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(CXVI) as a yellow amorphous solid (4.5 g, 14.1 mmol, 86.9% yield).ESIMS found for C₁₅H₁₈FN₅O₂ m/z 220.1 (M+H).

Step 4

To a solution ofN¹-(3-(2-amino-3-nitropyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(CXVI) (4.50 g, 10.43 mmol, 1.0 eq) in MeOH (15 mL) was added 10% Pd/C(540 mg, 15% by wt). The solution was purged with hydrogen and stirredfor 48 h at room temperature under hydrogen (15 psi). The suspension wasfiltered through Celite® and concentrated under vacuum and purified bysilica gel chromatography (MeOH:DCM=10:1) to produce4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)pyridine-2,3-diamine (CXVII) as a tan solid (750.0 mg, 2.59 mmol, 24.9%yield). ¹H NMR (CD₃OD, 400 MHz) δ ppm 2.32 (s, 6H), 2.60 (t, J=6.8 Hz,2H), 3.26 (t, J=6.8 Hz, 2H), 6.34-6.43 (m, 2H), 6.47 (d, J=5.6 Hz, 1H),7.58 (s, 1H), 7.75 (s, 1H); ESIMS found C₁₅H₂₀FN₅ m/z 290.1 (M+H).

Preparation of intermediateN-(3-(2,3-diaminopyridin-4-yl)-5-fluorobenzyl)methanesulfonamide(CXXIII) is depicted below in Scheme 24.

Step 1

A solution of 3-bromo-5-fluorobenzonitrile (CXVIII) (44.0 g, 220.0 mmol,1.0 eq) was dissolved in THF (30 mL). BH₃-Me₂S (33.43 g, 440.0 mmol, 2.0eq) was added to the solution at 20° C. Then it was stirred at 80° C.for 2 h, HCl (6 N, 100 mL) was added to the mixture slowly at 20° C. Themixture was stirred at 80° C. for 1 h, then it was washed with EtOAc(300 ml). The water phase was basified with 50% aqueous NaOH and it wasextracted with EtOAc (300 mL×3). The combined organic layers were driedover anhydrous Na₂SO₄ and concentrated in vacuo to produce(3-bromo-5-fluoro-phenyl)methanamine (CXIX) (24.0 g, 117.62 mmol, 53.5%yield). ¹HNMR (CDCl₃, 300 MHz) 3.86 (s, 2H), 7.01 (d, J=8 Hz, 1H), 7.12(d, J=8 Hz, 1H), 7.28 (s, 1H); ESIMS found C₇H₇BrFN m/z 203.9 (Br⁷⁹M+H).

Step 2

A solution of (3-bromo-5-fluoro-phenyl)methanamine (CXIX) (23.0 g, 112.7mmol, 1.0 eq) was dissolved in DCM (15 mL), TEA (34.22 g, 338.2 mmol,3.0 eq) was added to the mixture. Then MsCl (13.44 g, 117.3 mmol, 1.04eq) was added slowly to the solution at 0° C. It was stirred at 0-30° C.for 2 h. The reaction was washed with water and extracted with EtOAc.The combined organic layers were dried over anhydrous Na₂SO₄ andconcentrated to give N-(3-bromo-5-fluorobenzyl)methanesulfonamide (CXX)(34.0 g, 102.44 mmol, 90.9% yield, 85% purity) as an oil. ¹H NMR (CDCl₃,300 MHz) 2.88 (s, 3H), 4.24 (d, J=4.5 Hz, 2H), 6.99 (d, J=9 Hz, 1H),7.13 (dt, J=8.1 Hz, J=2 Hz, 1H), 7.25 (s, 1H); ESIMS found C₈H₉BrFNO₂Sm/z 282.0 (Br⁷⁹M+H).

Step 3

A solution of N-(3-bromo-5-fluorobenzyl)methanesulfonamide (CXX) (34.0g, 102.4 mmol, 1.0 eq) and4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane(52.02 g, 204.9 mmol, 2.0 eq), KOAc (20.11 g, 204.9 mmol, 2.0 eq) wasdissolved in dioxane (20 mL). Then Pd(dppf)Cl₂ (7.60 g, 10.2 mmol, 0.1eq) was added to the mixture. It was stirred at 90° C. for 2 h. Then thesolvent was removed to get the residue which was purified by silica gelcolumn (PE:EtOAc=10:1→100% EtOAc) to getN-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)methanesulfonamide(CXXI) (30.0 g, crude). ¹H NMR (CDCl₃, 400 MHz) 1.37 (s, 12H), 2.92 (s,3H), 4.34 (d, J=6.3 Hz, 2H), 7.19 (dt, J=9.3 Hz, J=2.1 Hz, 1H), 7.44(dd, J=8.7 Hz, J=2.4 Hz, 1H), 7.54 (s, 1H); ESIMS found C₁₄H₂₁BFNO₄S m/z330.1 (M+H).

Step 4

A solution ofN-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)methanesulfonamide (CXXI) (6.83 g, 20.75 mmol, 1.2 eq),4-chloro-3-nitropyridin-2-amine (XCV) (3.0 g, 17.29 mmol, 1.0 eq),Na₂CO₃ (6.41 g, 60.52 mmol) and Pd(dppf)Cl₂ (641.27 mg, 864.50 μmol) indioxane (40 mL) and H₂O (8 mL) was de-gassed and then heated to 80° C.overnight under N₂. TLC (PE:EtOAc=1:1) showed the starting material wasconsumed completely. The reaction mixture was poured into H₂O (300 mL).The mixture was extracted with EtOAc (3×250 mL). The organic phase waswashed with saturated brine (300 mL), dried over anhydrous NaSO₄,concentrated in vacuum to give a residue. The crude product was purifiedby silica gel chromatography (PE:EtOAc=10:1) to giveN-(3-(2-amino-3-nitropyridin-4-yl)-5-fluorobenzyl) methanesulfonamide(CXXII) (2.2 g, 6.46 mmol, 37.4% yield) as brown solid. ESIMS foundC₁₃H₁₃FN₄O₄S m/z 341.1 (M+H).

Step 5

A solution ofN-[[3-(4-amino-3-nitro-2-pyridyl)-5-fluoro-phenyl]methyl]methanesulfonamide(CXXII) (2.2 g, 6.46 mmol, 1.0 eq), Fe (1.44 g, 25.84 mmol, 4.0 eq) andNH₄Cl (2.8 g, 51.68 mmol, 8.0 eq) was dissolved in MeOH (30 mL). Themixture was stirred at 80° C. for 16 h. The mixture was cooled to roomtemperature and concentrated in reduced pressure at 60° C. The combinedorganic phase was washed with saturated brine (100 mL×2), dried overanhydrous Na₂SO₄, filtered and concentrated in vacuo to get crudeN-(3-(3,4-diaminopyridin-2-yl)-5-fluorobenzyl) methanesulfonamide(CXXIII) (1.60 g, 5.16 mmol, 79.8% yield) as brown solid. ¹H NMR (CD₃OD,400 MHz) 2.96 (s, 3H), 3.37 (s, 2H), 6.53 (d, J=4 Hz, 1H), 7.13 (d,J=8.8 Hz, 1H), 7.20 (d, J=9.2 Hz, 1H), 7.31 (s, 1H), 7.44 (d, J=4 Hz,1H); ESIMS found C₁₃H₁₅FN₄O₂S m/z 311.1 (M+H).

Example 1

Preparation ofN-isopropyl-5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine(90) is depicted below in Scheme 25.

Step 1

To a solution of 5-bromo-N-isopropylpyridin-3-amine (LII) (1.0 g, 4.65mmol, 1.0 eq) and5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carbaldehyde(XIV) (2.25 g, 5.58 mmol, 1.2 eq), Pd(dppf)Cl₂ (341 mg, 0.46 mmol, 0.10eq) and Na₂CO₃ (985 mg, 9.3 mmol, 2.0 eq) in dioxane (21 mL) and H₂O(3.5 mL) was de-gassed and then heated to 100° C. for 3 h under N₂. TLC(100% EtOAc) showed the starting material was consumed completely. Thereaction mixture was concentrated in vacuum to give a residue, which waspre-purified by silica gel column chromatography (PE:EtOAc=10:1→1:1) toafford pure5-(5-(isopropylamino)pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carbaldehyde(CXXIV) as a red brown oil (1.8 g, 4.38 mmol, 94.3% yield). ¹H NMR(CDCl₃, 400 MHz) δ ppm −0.03 (s, 9H), 0.93 (t, J=8.4 Hz, 2H), 1.29 (d,J=6 Hz, 6H), 1.76 (brs, 1H), 3.62 (t, J=8.4 Hz, 2H), 3.71-3.82 (m, 1H),5.86 (s, 2H), 7.10 (t, J=2 Hz, 1H), 7.73 (s, 1H), 8.01 (d, J=2.4 Hz,1H), 8.22 (s, 1H), 8.49 (s, 1H), 10.29 (s, 1H); ESIMS found forC₂₂H₃₀N₄O₂Si m/z 411.1 (M+H).

Step 2-3

A solution of 5-(5-(isopropylamino)pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carbaldehyde (CXXIV) (100.0 mg, 0.24 mmol,1.0 eq), [3,4′-bipyridine]-2′,3′-diamine (LXXXVII) (45 mg, 0.24 mmol,1.0 eq) and Na₂S₂O₅ (53 mg, 0.29 mmol, 1.20 eq) in DMF (2 mL) wasstirred at 120° C. for 20 h. LC/MS showed the starting material wasconsumed. Water (5 mL) was then added dropwise to the mixture andstirred at room temperature for 10 min, the mixture was filtered, thenthe filtrate was washed by H₂O (2 mL×3), dried over anhydrous MgSO₄, andevaporated under vacuum to give crudeN-isopropyl-5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)pyridin-3-amine (CXXV). CXXV wasdissolved in dry DCM (5 mL) before adding triethylsilane (92 μL, 0.57mmol) and TFA (2.5 mL). The reaction was stirred at room temperature for2 h under N₂. The solvent was evaporated under reduced pressure; theresidue was taken up water (10 mL), and basified with 5N NH₄OH. Theprecipitates were filtered, washed by cold water and dried under vacuumat room temperature. The crude product was suspended in DCM (10 mL),sonicated briefly and then heated to boiling for 5 min. The solution wascooled to room temperature and the solids were filtered, washed with DCMand dried under vacuum at room temperature to produceN-isopropyl-5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine(90) as a white solid (43.9 mg, 0.10 mmol, 41.0%). ¹H NMR (DMSO-d₆, 400MHz) 1.23 (d, J=6.27 Hz, 6H), 3.80-3.91 (m, 1H), 7.88 (d, J=5.27 Hz,1H), 7.90 (s, 2H), 8.02 (brs, 1H), 8.10 (d, J=2.01 Hz, 1H), 8.26-8.35(m, 1H), 8.50 (s, 1H), 8.56 (d, J=5.27 Hz, 1H), 8.86 (s, 1H), 9.03 (d,J=5.52 Hz, 1H), 9.44-9.55 (m, 1H), 9.93-10.00 (m, 1H), 14.32 (brs, 1H);ESIMS found for C₂₆H₂₂N₈ m/z 447.3 (M+1).

The following compounds were prepared in accordance with the proceduredescribed in the above Example 1.

N-(5-(3-(7-(3-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide1.

White solid (38.5 mg, 0.08 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.14(t, J=7.53 Hz, 3H), 2.41-2.47 (m, 2H), 7.33 (td, J=8.16, 2.26 Hz, 1H),7.60-7.68 (m, 1H), 7.70 (d, J=5.27 Hz, 1H), 7.82-7.92 (m, 2H), 8.30-8.39(m, 1H), 8.43 (d, J=5.52 Hz, 1H), 8.45-8.54 (m, 1H), 8.66 (brs, 1H),8.82 (s, 1H), 8.91 (s, 1H), 8.94 (d, J=1.00 Hz, 1H), 10.64 (brs, 1H),14.09 (brs, 1H); ESIMS found for C₂₇H₂₀FN₇O m/z 478.2 (M+1).

N-(5-(3-(7-(3-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide2.

White solid (18.8 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 0.98(d, J=7 Hz, 6H), 2.12 (non, J=6.75 Hz, 1H), 2.28 (d, J=7 Hz, 2H), 7.30(td, J=2 Hz, J=8 Hz, 1H), 7.63 (q, J=8 Hz, 1H), 7.70 (d, J=5 Hz, 1H),7.81 (dd, J=1.5 Hz, J=8.5 Hz, 1H), 7.85 (d, J=8.5 Hz, 1H), 8.38 (d, J=8Hz, 1H), 8.42 (d, J=5.5 Hz, 1H), 8.49 (s, 1H), 8.54 (d, J=11 Hz, 1H),8.58 (d, J=2 Hz, 1H), 8.77 (d, J=2 Hz, 1H), 8.89 (s, 1H), 10.21 (s, 1H),13.93 (s, 1H); ESIMS found for C₂₉H₂₄FN₇O m/z 506.2 (M+1).

5-(3-(7-(3-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N,N-dimethylpyridin-3-amine7.

White solid (46.0 mg, 0.10 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 3.14(s, 6H), 7.35 (td, J=8.34, 1.88 Hz, 1H), 7.62-7.72 (m, 2H), 7.84-7.90(m, 2H), 7.92-7.98 (m, 1H), 8.23 (d, J=2.51 Hz, 1H), 8.30-8.38 (m, 1H),8.43 (d, J=5.27 Hz, 1H), 8.47 (s, 1H), 8.48-8.56 (m, 1H), 8.91 (s, 1H),13.99 (brs, 1H), 14.12 (s, 1H); ESIMS found for C₂₆H₂₀FN₇ m/z 450.3(M+1).

N-(5-(3-(7-(3-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide9.

White solid (15.1 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 1.16(d, J=7 Hz, 6H), 2.64-2.72 (m, 1H), 7.30 (td, J=2.5 Hz, J=8 Hz, 1H),7.63 (q, J=8 Hz, 1H), 7.70 (d, J=5 Hz, 1H), 7.82 (dd, J=1.5 Hz, J=9 Hz,1H), 7.85 (d, J=9 Hz, 1H), 8.40 (d, J=8 Hz, 1H), 8.42 (d, J=5.5 Hz, 1H),8.52 (t, J=2.5 Hz, 1H), 8.55 (d, J=10 Hz, 1H), 8.68 (d, J=2 Hz, 1H),8.79 (d, J=2.5 Hz, 1H), 8.89 (s, 1H), 10.18 (s, 1H), 13.93 (s, 1H);ESIMS found for C₂₈H₂₂FN₇O m/z 492.1 (M+1).

1-(5-(3-(7-(3-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine13.

White solid (58.7 mg, 0.13 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.79(d, J=4.27 Hz, 6H), 4.51 (d, J=4.77 Hz, 2H), 7.40 (td, J=8.53, 2.01 Hz,1H), 7.64-7.70 (m, 1H), 7.71 (d, J=5.27 Hz, 1H), 7.88-7.94 (m, 1H), 8.00(dd, J=8.78, 1.76 Hz, 1H), 8.28 (d, J=6.52 Hz, 1H), 8.46-8.52 (m, 1H),8.49 (d, J=4.02 Hz, 1H), 8.75 (s, 1H), 8.92 (d, J=1.76 Hz, 1H), 8.96 (s,1H), 9.22 (d, J=2.01 Hz, 1H), 11.34 (brs, 1H), 14.21 (brs, 1H); ESIMSfound for C₂₇H₂₂FN₇ m/z 464.3 (M+1).

N-(5-(3-(7-(3-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide19.

White solid (15.3 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm0.85-1.00 (m, 4H), 1.88-1.98 (m, 1H), 7.29-7.39 (m, 1H), 7.61-7.70 (m,1H), 7.70-7.76 (m, 1H), 7.85-7.95 (m, 2H), 8.25-8.36 (m, 1H), 8.37-8.54(m, 2H), 8.77-8.85 (m, 1H), 8.93 (d, J=0.75 Hz, 1H), 8.94-9.03 (m, 1H),9.05-9.16 (m, 1H), 11.27 (brs, 1H), 14.16 (brs, 1H); ESIMS found forC₂₈H₂₀FN₇O m/z 490.2 (M+1).

N-(5-(3-(7-(3-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide21.

White solid (12.2 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.55-1.65 (m, 2H), 1.65-1.74 (m, 2H), 1.75-1.85 (m, 2H), 1.89-2.00 (m,2H), 2.93 (quin, J=7.92 Hz, 1H), 7.31 (td, J=8.60, 1.76 Hz, 1H),7.62-7.70 (m, 1H), 7.72 (d, J=5.14 Hz, 1H), 7.85-7.96 (m, 2H), 8.25-8.34(m, 1H), 8.39-8.55 (m, 2H), 8.85 (brs, 1H), 8.92 (s, 1H), 8.96 (brs,1H), 9.15 (brs, 1H), 10.96 (brs, 1H), 14.19 (brs, 1H); ESIMS found forC₃₀H₂₄FN₇O m/z 518.1 (M+1).

2-(5-(5-((3,3-Difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridine25.

White solid (44.7 mg, 0.09 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm2.36-2.51 (m, 4H), 2.56-2.67 (m, 2H), 4.49-4.63 (m, 2H), 7.39 (td,J=8.60, 2.89 Hz, 1H), 7.63-7.74 (m, 2H), 7.90 (d, J=8.78 Hz, 1H),7.96-8.02 (m, 1H), 8.31 (dt, J=7.09, 1.10 Hz, 1H), 8.46 (d, J=5.27 Hz,1H), 8.49-8.60 (m, 1H), 8.67 (s, 1H), 8.88 (s, 1H), 8.97 (s, 1H), 9.18(d, J=2.01 Hz, 1H), 14.12 (brs, 1H); ESIMS found for C₂₉H₂₂F₃N₇ m/z526.3 (M+1).

N-(5-(3-(7-(4-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide28.

White solid (13.0 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.98(d, J=6.53 Hz, 6H), 2.15 (non, J=6.76 Hz, 1H), 2.31 (d, J=7.03 Hz, 2H),7.36-7.48 (m, 2H), 7.59-7.66 (m, 1H), 7.81-7.88 (m, 1H), 7.88-8.07 (m,1H), 8.40 (t, J=5.04 Hz, 1H), 8.56-8.66 (m, 3H), 8.66-8.77 (m, 2H), 8.88(d, J=11.8 Hz, 1H), 10.32 (s, 1H), 13.93 (brs, 2H); ESIMS found forC₂₉H₂₄FN₇O m/z 506.1 (M+1).

N-(5-(3-(7-(4-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide34.

White solid (10.0 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 300 MHz) δ ppm 1.30(s, 9H), 5.94 (s, 1H), 7.41 (t, J=8.85 Hz, 2H), 7.62 (d, J=5.27 Hz, 1H),7.94 (dd, J=8.85, 1.32 Hz, 1H), 8.04 (d, J=8.67 Hz, 1H), 8.37-8.46 (m,1H), 8.63 (d, J=5.65 Hz, 2H), 8.70 (s, 1H), 8.72-8.79 (m, 1H), 8.85-8.93(m, 1H), 8.98 (d, J=1.88 Hz, 1H), 9.74 (s, 1H), 13.98 (brs, 2H); ESIMSfound for C₂₉H₂₄FN₇O m/z 506.2 (M+1).

7-(4-Fluorophenyl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine40.

White solid (23.6 mg, 0.05 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.82-1.94 (m, 2H), 2.02-2.14 (m, 2H), 3.15-3.28 (m, 2H), 3.44-3.55 (m,2H), 4.56 (d, J=5.52 Hz, 2H), 7.44 (t, J=8.76 Hz, 2H), 7.61 (d, J=5.31Hz, 1H), 7.85-7.95 (m, 2H), 8.40 (d, J=1.00 Hz, 1H), 8.43 (d, J=5.02 Hz,1H), 8.52-8.69 (m, 2H), 8.75-8.81 (m, 1H), 8.96 (s, 1H), 9.13-9.18 (m,1H), 9.85-10.01 (m, 1H), 13.99 (brs, 1H); ESIMS found for C₂₉H₂₄FN₇ m/z490.2 (M+1).

N-(5-(3-(7-(4-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide46.

White solid (12.0 mg, 0.02 mmol). ¹H NMR (CD₃OD, 400 MHz) δ ppm δ1.94-2.06 (m, 1H), 2.08-2.21 (m, 1H), 2.29-2.40 (m, 2H), 2.41-2.53 (m,2H), 3.47 (quin, J=8.52 Hz, 1H), 7.48 (t, J=8.78 Hz, 2H), 7.82 (d,J=6.27 Hz, 1H), 7.96 (d, J=1.00 Hz, 2H), 8.11 (dd, J=8.03, 4.77 Hz, 2H),8.63 (d, J=6.02 Hz, 1H), 8.98 (d, J=5.27 Hz, 2H), 9.02 (t, J=1.88 Hz,1H), 9.32 (d, J=2.01 Hz, 1H); ESIMS found for C₂₉H₂₂FN₇O m/z 504.1(M+1).

7-(4-Fluorophenyl)-2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine52.

White solid (167.2 mg, 0.41 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 7.41(t, J=9.04 Hz, 2H), 7.61 (d, J=5.27 Hz, 1H), 7.87 (d, J=8.53 Hz, 1H),7.97 (dd, J=8.56 Hz, J=1.52 Hz, 1H), 8.41 (d, J=5.27 Hz, 1H), 8.64 (dd,J=9.03, 5.52 Hz, 2H), 9.01 (s, 1H), 9.26 (s, 1H), 9.29 (s, 2H), 13.91(brs, 1H), 13.96 (brs, 1H); ESIMS found for C₂₃H₁₄FN₇ m/z 408.0 (M+1).

5-(3-(7-(2-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine55.

White solid (7.9 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm7.46-7.53 (m, 2H), 7.56 (d, J=5.27 Hz, 1H), 7.59-7.67 (m, 1H), 7.85 (dd,J=8.80 Hz, J=1.76 Hz, 1H), 7.91 (d, J=8.52 Hz, 1H), 7.97 (s, 1H),8.00-8.07 (m, 1H), 8.09 (d, J=2.26 Hz, 1H), 8.39 (s, 1H), 8.56 (d,J=4.27 Hz, 1H), 8.79 (s, 1H), 14.36 (brs, 1H); ESIMS found for C₂₄H₁₆FN₇m/z 422.1 (M+1).

5-(3-(7-(2-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N,N-dimethylpyridin-3-amine59.

White solid (11.0 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 3.17(s, 6H), 7.44-7.52 (m, 3H), 7.57-7.65 (m, 1H), 7.88 (d, J=8.66 Hz, 1H),7.94 (brs, 1H), 7.98 (dd, J=8.72, 1.57 Hz, 1H), 8.07 (brs, 1H), 8.23 (d,J=2.51 Hz, 1H), 8.44 (s, 1H), 8.51 (d, J=4.89 Hz, 1H), 8.81 (s, 1H),14.24 (brs, 1H); ESIMS found for C₂₆H₂₀FN₇ m/z 450.1 (M+1).

N-(5-(3-(7-(2-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide61.

White solid (18.9 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.18(d, J=6.78 Hz, 5H), 2.66-2.77 (m, 1H), 7.38-7.50 (m, 3H), 7.51-7.60 (m,1H), 7.77-7.87 (m, 2H), 8.34 (s, 1H), 8.40-8.47 (m, 1H), 8.47-8.54 (m,1H), 8.63 (s, 1H), 8.78 (s, 2H), 10.27 (s, 1H); ESIMS found forC₂₈H₂₂FN₇O m/z 492.2 (M+1).

N-(5-(3-(7-(2-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide68.

White solid (24.0 mg, 0.05 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.07(m, 9H), 2.29 (s, 2H), 7.32-7.50 (m, 3H), 7.51-7.60 (m, 1H), 7.74-7.87(m, 2H), 8.25-8.36 (m, 1H), 8.38-8.52 (m, 2H), 8.59-8.67 (m, 1H), 8.73(brs, 1H), 8.77 (s, 1H), 10.16-10.29 (m, 1H), 13.93 (brs, 2H); ESIMSfound for C₃₀H₂₆FN₇O m/z 520.3 (M+1).

N-(5-(3-(7-(2-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide71.

White solid (14.9 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.88(d, J=5.65 Hz, 4H), 1.87-1.97 (m, 1H), 7.36-7.50 (m, 3H), 7.55 (brs,1H), 7.74-7.88 (m, 2H), 8.32 (brs, 1H), 8.40-8.51 (m, 2H), 8.62 (brs,1H), 8.71-8.85 (m, 2H), 10.74 (brs, 1H), 13.88 (brs, 1H); ESIMS foundfor C₂₈H₂₀FN₇O m/z 490.1 (M+1).

N-(5-(3-(7-(2-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide73.

White solid (12.0 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.53-1.64 (m, 2H), 1.65-1.74 (m, 2H), 1.74-1.85 (m, 2H), 1.87-1.98 (m,2H), 2.88 (quin, J=7.8 Hz, 1H), 7.37-7.50 (m, 3H), 7.51-7.59 (m, 1H),7.75-7.86 (m, 2H), 8.27-8.37 (m, 1H), 8.38-8.46 (m, 1H), 8.46-8.53 (m,1H), 8.62 (brs, 1H), 8.70-8.76 (m, 1H), 8.78 (s, 1H), 10.25-10.34 (m,1H), (13.93 (brs, 2H); ESIMS found for C₃₀H₂₄FN₇O m/z 518.2 (M+1).

5-(3-(7-(Pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine 81.

White solid (5.0 mg, 0.01 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 7.82(d, J=5.02 Hz, 1H), 7.84-7.93 (m, 2H), 8.05-8.16 (m, 3H), 8.51 (s, 1H),8.53 (d, J=5.14 Hz, 1H), 8.88 (s, 1H), 8.93 (d, J=4.39 Hz, 1H), 9.30(brs, 1H), 9.86 (brs, 1H), 14.20 (brs, 1H); ESIMS found for C₂₃H₁₆N₈ m/z405.0 (M+1).

7-(Pyridin-3-yl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine82.

White solid (18.9 mg, 0.05 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 7.88(d, J=5.02 Hz, 1H), 7.92 (d, J=9.03 Hz, 1H), 8.03 (dd, J=8.78, 1.51 Hz,1H), 8.23 (dd, J=8.16, 5.65 Hz, 1H), 8.29 (dd, J=7.91, 5.65 Hz, 1H),8.55 (d, J=5.02 Hz, 1H), 8.94 (d, J=5.52 Hz, 1H), 8.99 (d, J=0.75 Hz,1H), 9.00-9.07 (m, 2H), 9.44 (d, J=1.51 Hz, 1H), 9.46-9.53 (m, 1H),10.02 (brs, 1H), 14.32 (brs, 1H); ESIMS found for C₂₃H₁₅N₇ m/z 390.0(M+1).

N-(5-(3-(7-(Pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide87.

White solid (84.4 mg, 0.18 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.18(d, J=6.78 Hz, 6H), 2.65-2.74 (m, 1H), 7.59-7.67 (m, 1H), 7.73 (d,J=5.02 Hz, 1H), 7.79-7.88 (m, 2H), 8.45 (d, J=5.02 Hz, 1H), 8.53 (brs,1H), 8.68 (brs, 2H), 8.79 (d, J=1.25 Hz, 1H), 8.86 (s, 1H), 8.97-9.03(m, 1H), 9.59 (s, 1H), 10.25 (s, 1H), 13.97 (s, 1H), 13.98 (s, 1H);ESIMS found for C₂₇H₂₂N₈O m/z 475.1 (M+1).

2-(5-(5-(Piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridine93.

White solid (29.8 mg, 0.06 mmol). ¹H NMR (CD₃OD, 400 MHz) δ ppm1.53-1.68 (m, 1H), 1.85-2.04 (m, 5H), 3.13-3.27 (m, 2H), 3.61-3.72 (m,2H), 4.76 (s, 2H), 7.95 (d, J=8.78 Hz, 1H), 7.99 (d, J=5.77 Hz, 1H),8.10 (d, J=8.78 Hz, 1H), 8.38-8.45 (m, 1H), 8.75 (d, J=5.77 Hz, 1H),9.10-9.16 (m, 2H), 9.17 (s, 1H), 9.31 (d, J=8.28 Hz, 1H), 9.48 (s, 2H),9.83 (s, 1H); ESIMS found for C₂₉H₂₆N₈ m/z 487.3 (M+1).

N-Benzyl-1-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine101.

White solid (35.2 mg, 0.07 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 4.31(brs, 2H), 4.52 (brs, 2H), 7.38-7.49 (m, 2H), 7.61 (d, J=7.78 Hz, 2H),7.81-7.87 (m, 1H), 7.92 (d, J=8.78 Hz, 1H), 8.01 (d, J=8.78 Hz, 1H),8.07-8.17 (m, 1H), 8.54 (d, J=5.02 Hz, 1H), 8.84-9.01 (m, 3H), 9.22-9.39(m, 2H), 9.90-10.12 (m, 3H), 14.21 (brs, 1H); ESIMS found for C₃₁H₂₄N₈m/z 509.3 (M+1).

2-(5-(4-Methylpyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine109.

White solid (40.9 mg, 0.10 mmol). ¹H NMR (CD₃OD, 400 MHz) δ ppm 2.70 (s,3H), 7.66 (dd, J=8.66, 1.63 Hz, 1H), 7.89-7.97 (m, 2H), 8.14 (d, J=6.02Hz, 1H), 8.68 (d, J=5.77 Hz, 1H), 8.71 (dd, J=1.51, 0.75 Hz, 1H), 8.80(dd, J=6.02, 0.75 Hz, 1H), 8.90 (s, 1H), 8.95 (d, J=6.78 Hz, 2H), 9.10(d, J=6.78 Hz, 2H); ESIMS found for C₂₄H₁₇N₇ m/z 404.2 (M+1).

2-Phenyl-N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide114.

White solid (4.7 mg, 0.01 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 3.87(s, 2H), 7.22-7.29 (m, 1H), 7.30-7.37 (m, 2H), 7.40 (s, 1H), 7.42 (d,J=1.25 Hz, 1H), 7.87-7.96 (m, 3H), 8.57 (d, J=5.02 Hz, 1H), 8.85 (dd,J=3.26, 1.51 Hz, 1H), 8.91 (s, 1H), 8.94 (brs, 1H), 8.97-9.08 (m, 3H),9.08-9.15 (m, 2H), 11.26 (brs, 1H), 14.20 (brs, 2H); ESIMS found forC₃₁H₂₂N₈O m/z 523.2 (M+1).

N-(5-(3-(7-(Pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide121.

White solid (10.7 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.96(t, J=7.40 Hz, 3H), 1.68 (sxt, J=7.28 Hz, 2H), 2.51-2.58 (m, 2H), 7.92(s, 2H), 7.94 (d, J=5.52 Hz, 1H), 8.58 (d, J=5.02 Hz, 1H), 8.89 (brs,1H), 8.92 (s, 1H), 8.97 (s, 1H), 9.02 (d, J=1.00 Hz, 1H), 9.04-9.12 (m,4H), 10.98 (brs, 1H), 14.22 (brs, 1H); ESIMS found for C₂₇H₂₂N₈O m/z475.2 (M+1).

N-(5-(3-(7-(Pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide126.

White solid (30.0 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.14-1.39 (m, 4H), 1.39-1.54 (m, 2H), 1.64-1.72 (m, 1H), 1.75-1.84 (m,2H), 1.89-1.98 (m, 2H), 7.87-7.98 (m, 3H), 8.59 (d, J=5.27 Hz, 1H), 8.93(s, 2H), 9.01 (s, 1H), 9.09 (brs, 5H), 10.95 (brs, 1H), 14.24 (brs, 1H);ESIMS found for C₃₀H₂₆N₈O m/z 515.2 (M+1).

N-((5-(3-(7-(Pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine136.

White solid (20.7 mg, 0.05 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.28(t, J=7.15 Hz, 3H), 3.00-3.12 (m, 2H), 4.36-4.44 (m, 2H), 7.64 (ddd,J=7.28 Hz, J=5.28 Hz, J=0.76 Hz, 1H), 7.94 (d, J=8.76 Hz, 1H), 8.03 (dd,J=8.56 Hz, J=1.76 Hz, 1H), 8.15 (d, J=5.27 Hz, 1H), 8.22 (dt, J=7.76 Hz,J=2.00 Hz, 1H), 8.57 (d, J=5.27 Hz, 1H), 8.86 (d, J=1.25 Hz, 1H),8.91-8.96 (m, 2H), 9.00 (s, 1H), 9.10-9.22 (m, 1H), 9.28 (d, J=1.51 Hz,1H), 9.54-9.65 (m, 2H), 14.27 (brs, 1H); ESIMS found for C₂₆H₂₂N₈ m/z447.1 (M+1).

N-(5-(3-(7-(Pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide141.

White solid (18.0 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm7.36-7.44 (m, 1H), 7.59-7.68 (m, 2H), 7.68-7.75 (m, 1H), 7.91-8.00 (m,2H), 8.10 (d, J=8.03 Hz, 3H), 8.14 (d, J=5.27 Hz, 1H), 8.54 (d, J=5.52Hz, 1H), 8.86 (d, J=4.02 Hz, 1H), 8.97-9.04 (m, 3H), 9.23 (s, 2H), 11.04(s, 1H), 14.17 (brs, 1H); ESIMS found for C₃₀H₂₀N₈O m/z 509.2 (M+1).

N-(5-(3-(7-(Pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide148.

White solid (38.7 mg, 0.08 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.93(t, J=7.40 Hz, 3H), 1.39 (sxt, J=7.52 Hz, 2H), 1.65 (quin, J=7.52 Hz,2H), 2.42-2.50 (m, 11H), 7.56 (dd, J=7.04 Hz, J=4.28 Hz, 1H), 7.86-7.96(m, 2H), 8.09-8.19 (m, 2H), 8.54 (d, J=5.52 Hz, 1H), 8.79 (s, 1H), 8.89(d, J=4.27 Hz, 1H), 8.93 (s, 2H), 9.02 (s, 1H), 9.15-9.31 (m, 1H), 10.81(brs, 1H), 14.16 (brs, 1H); ESIMS found for C₂₈H₂₄N₈O m/z 489.2 (M+1).

N-(5-(3-(7-(Pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide 150.

White solid (48.0 mg, 0.10 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.79-1.92 (m, 1H), 1.93-2.06 (m, 1H), 2.13-2.23 (m, 2H), 2.24-2.36 (m,2H), 7.49 (brs, 1H), 7.86 (s, 2H), 8.06 (t, J=7.28 Hz, 1H), 8.16 (brs,1H), 8.48 (brs, 1H), 8.65-8.78 (m, 3H), 8.82 (brs, 1H), 8.90-8.98 (m,1H), 9.49 (brs, 1H), 10.20 (s, 1H), 13.92 (brs, 1H); ESIMS found forC₂₈H₂₂N₈O m/z 487.1 (M+1).

1-Cyclopentyl-N-((5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine154.

White solid (52.4 mg, 0.10 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.22-1.34 (m, 2H), 1.48-1.56 (m, 2H), 1.57-1.66 (m, 2H), 1.76-1.86 (m,2H), 2.22-2.31 (m, 1H), 2.95-3.03 (m, 2H), 4.39-4.46 (m, 2H), 7.60-7.67(m, 1H), 7.93-7.98 (m, 1H), 8.02-8.07 (m, 1H), 8.15 (d, J=5.27 Hz, 1H),8.19-8.27 (m, 1H), 8.57 (d, J=5.02 Hz, 1H), 8.92 (brs, 2H), 8.97 (s,1H), 9.01 (s, 1H), 9.30 (s, 1H), 9.49-9.59 (m, 2H), 14.28 (brs, 1H);ESIMS found for C₃₀H₂₈N₈ m/z 501.2 (M+1).

N-(5-(3-(7-(Piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide157.

White solid (23.6 mg, 0.05 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.13(t, J=7.53 Hz, 3H), 1.59-1.77 (m, 6H), 2.41 (q, J=7.36 Hz, 2H),3.96-4.06 (m, 4H), 7.74-7.83 (m, 2H), 7.93 (d, J=5.77 Hz, 1H), 8.23 (s,1H), 8.56 (d, J=2.01 Hz, 1H), 8.63 (dd, J=7.78, 2.26 Hz, 2H), 8.78 (s,1H), 10.25 (s, 1H), 13.70 (brs, 2H); ESIMS found for C₂₆H₂₆N₈O m/z 467.3(M+1).

N,N-Dimethyl-5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine163.

White solid (16.3 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.75(brs, 6H), 3.12 (s, 6H), 4.17-4.44 (m, 4H), 6.87-6.96 (m, 1H), 7.72(brs, 1H), 7.86 (d, J=8.76 Hz, 1H), 7.94 (dd, J=8.53, 1.25 Hz, 1H),7.96-8.03 (m, 1H), 8.21 (d, J=2.26 Hz, 1H), 8.36 (s, 1H), 8.66 (s, 1H),14.05 (brs, 1H); ESIMS found for C₂₅H₂₆N₈ m/z 439.1 (M+1).

N,N-Dimethyl-1-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine169.

White solid (9.8 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.77(brs, 6H), 2.78 (d, J=4.27 Hz, 6H), 4.45 (d, J=3.26 Hz, 2H), 6.97 (d,J=7.53 Hz, 1H), 7.90 (d, J=8.80 Hz, 1H), 7.97 (dd. J=9.04 Hz, J=0.76 Hz,2H), 8.61 (brs, 1H), 8.69 (s, 1H), 8.80 (s, 1H), 9.06 (s, 1H), 11.26(brs, 1H), 14.19 (brs, 1H), 14.87 (brs, 1H); ESIMS found for C₂₆H₂₈N₈m/z 453.2 (M+1).

N-(5-(3-(7-(Piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide175.

White solid (13.7 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm0.86-0.96 (m, 4H), 1.75 (brs, 6H), 1.93-2.02 (m, 1H), 6.95 (d, J=7.28Hz, 1H), 7.89 (s, 2H), 7.92-8.02 (m, 1H), 8.64 (s, 1H), 8.83 (brs, 1H),8.87-8.98 (m, 2H), 11.40 (brs, 1H), 14.21 (brs, 1H), 14.84 (brs, 1H);ESIMS found for C₂₇H₂₆N₈O m/z 479.2 (M+1).

2-(5-(5-((3,3-Difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridine181.

White solid (42.4 mg, 0.08 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.77(brs, 6H), 2.56-2.66 (m, 2H), 3.46-3.62 (m, 2H), 4.48-4.61 (m, 2H), 6.97(d, J=7.53 Hz, 1H), 7.88-7.93 (m, 1H), 7.94-8.02 (m, 1H), 7.98 (dd,J=8.66, 1.63 Hz, 1H), 8.66 (brs, 1H), 8.69 (s, 1H), 8.84 (s, 1H), 9.06(d, J=1.76 Hz, 1H), 14.19 (brs, 1H), 14.85 (brs, 1H); ESIMS found forC₂₈H₂₈F₂N₈ m/z 515.2 (M+1).

3-Methyl-N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide184.

White solid (14.5 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.968(d, J=6.80 Hz, 6H), 2.12 (non, J=6.80 Hz, 1H), 2.24 (s, 3H), 2.29 (d,J=7.2 Hz, 2H), 7.64 (d, J=5.2 Hz, 1H), 7.79-7.90 (m, 2H), 8.30 (s, 1H),8.39 (d, J=5.2 Hz, 1H), 8.49 (s, 1H), 8.69 (d, J=2.0 Hz, 1H), 8.82 (s,1H), 8.84 (d, J=2.0 Hz, 1H), 9.00 (s, 1H), 10.41 (s, 1H), 14.12 (brs,2H); ESIMS found for C₂₇H₂₅N₉O m/z 492.2 (M+1).

N-(5-(3-(7-(4-Methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide190.

White solid (41.1 mg, 0.08 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.28(s, 9H), 2.23 (s, 3H), 7.62 (d, J=5.40 Hz, 1H), 7.78-7.89 (m, 2H), 8.26(s, 1H), 8.38 (d, J=5.40 Hz, 1H), 8.50 (t, J=2.13 Hz, 1H), 8.69 (d,J=1.88 Hz, 1H), 8.83 (s, 1H), 8.93 (d, J=2.26 Hz, 1H), 9.01 (s, 1H),9.56 (s, 1H), 13.99 (brs, 2H); ESIMS found for C₂₇H₂₅N₉O m/z 492.2(M+1).

N-(5-(3-(7-(4-Methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide202.

White solid (66.3 mg, 0.14 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.75-1.90 (m, 1H), 1.92-2.04 (m, 1H), 2.10-2.36 (m, 4H), 2.22 (s, 3H),3.23-3.32 (m, 1H), 7.62 (d, J=5.14 Hz, 1H), 7.77-7.91 (m, 2H), 8.29(brs, 1H), 8.38 (d, J=5.14 Hz, 1H), 8.49 (brs, 1H), 8.68 (s, 1H), 8.82(d, J=2.89 Hz, 2H), 8.98 (brs, 1H), 10.14 (s, 1H), 13.99 (brs, 2H);ESIMS found for C₂₇H₂₃N₉O m/z 490.2 (M+1).

5-(3-(7-(4-Methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine211.

White solid (7.7 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.91(brs, 3H), 3.69-3.78 (m, 4H), 3.80-3.89 (m, 4H), 7.00-7.07 (m, 1H), 7.85(dd, J=8.52 Hz, J=1.52 Hz, 1H), 7.91 (d, J=8.76 Hz, 1H), 7.98 (s, 1H),8.07 (d, J=2.26 Hz, 1H), 8.13-8.21 (m, 1H), 8.43 (brs, 1H), 8.64 (s,1H), 11.42 (brs, 1H), 14.30 (brs, 1H); ESIMS found for C₂₃H₂₃N₉ m/z426.1 (M+1).

N-(5-(3-(7-(4-Methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide217.

White solid (20.3 mg, 0.04 mmol). ¹H NMR (CD₃OD, 400 MHz) δ ppm 1.30 (d,J=6.78 Hz, 5H), 2.82 (spt, J=7.28 Hz, 2H), 3.04 (s, 3H), 3.23-3.35 (m,2H), 3.43-3.57 (m, 2H), 3.80-4.04 (m, 4H), 7.12 (d, J=7.28 Hz, 1H), 7.92(d, J=1.00 Hz, 2H), 8.09-8.18 (m, 1H), 8.76-8.83 (m, 1H), 8.98 (d,J=1.25 Hz, 1H), 9.03 (t, J=1.88 Hz, 1H), 9.28 (d, J=1.76 Hz, 1H); ESIMSfound for C₂₇H₂₉N₉O m/z 496.3 (M+1).

7-(4-Methylpiperazin-1-yl)-2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine223.

White solid (17.3 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.34-1.47 (m, 2H), 1.65-1.76 (m, 2H), 1.77-1.88 (m, 4H), 2.82-2.89 (m,3H), 2.91-3.03 (m, 2H), 3.63-3.73 (m, 4H), 3.82-3.95 (m, 2H), 4.47 (d,J=5.02 Hz, 2H), 7.01-7.11 (m, 1H), 7.90 (d, J=8.78 Hz, 1H), 8.01 (d,J=8.53 Hz, 1H), 8.11-8.22 (m, 1H), 8.68-8.78 (m, 2H), 8.83 (s, 1H), 9.13(brs, 1H), 11.16 (brs, 1H), 11.54 (brs, 1H), 14.23 (brs, 1H); ESIMSfound for C₂₉H₃₃N₉ m/z 508.2 (M+1).

N-(5-(3-(7-(4-Methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide229.

White solid (32.7 mg, 0.06 mmol). ¹H NMR (CD₃OD, 400 MHz) δ ppm1.65-1.76 (m, 2H), 1.76-1.86 (m, 2H), 1.87-1.98 (m, 2H), 1.99-2.11 (m,2H), 3.02 (quin, J=8.04 Hz, 4H), 3.04 (s, 3H), 3.24-3.33 (m, 2H),3.44-3.57 (m, 2H), 3.79-4.04 (m, 4H), 7.09-7.15 (m, 1H), 7.91 (d, J=1.00Hz, 2H), 8.09-8.19 (m, 1H), 8.76-8.83 (m, 1H), 8.97 (d, J=1.26 Hz, 1H),9.00 (t, J=1.88 Hz, 1H), 9.30 (d, J=1.76 Hz, 1H); ESIMS found forC₂₉H₃₁N₉O m/z 522.3 (M+1).

7-(4-Methylpiperazin-1-yl)-2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine234.

White solid (54.6 mg, 0.13 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.85(brs, 3H), 3.26-3.41 (m, 4H), 3.76-3.91 (m, 4H), 7.03-7.12 (m, 1H),7.88-7.94 (m, 1H), 7.94-8.00 (m, 1H), 8.13-8.26 (m, 1H), 8.67 (brs, 1H),9.25 (d, J=3.01 Hz, 3H), 11.34 (brs, 1H), 14.25 (brs, 1H); ESIMS foundfor C₂₂H₂₁N₉ m/z 412.1 (M+1).

2-(5-(Pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine 238.

White solid (66.2 mg, 0.21 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm7.46-7.52 (m, 1H), 7.90-8.02 (m, 3H), 8.27 (d, J=8.28 Hz, 1H), 8.53 (d,J=5.27 Hz, 1H), 8.65-8.73 (m, 1H), 8.83 (d, J=0.75 Hz, 2H), 9.24 (d,J=1.51 Hz, 1H); ESIMS found for C₁₈H₁₂N₆ m/z 313.1 (M+1).

2-(5-(4-Methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine239.

Light brown solid (21.1 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 300 MHz) δ ppm2.31 (s, 3H), 7.24 (dd, J=8.01, 4.80 Hz, 1H) 7.39 (d, J=5.09 Hz, 1H)7.52 (dd, J=8.57, 1.41 Hz, 1H) 7.78 (d, J=8.67 Hz, 1H) 8.35 (d, J=3.96Hz, 1H) 8.48 (t, J=4.33 Hz, 3H); ESIMS found for C₁₉H₁₄N₆ m/z 327.6(M+1).

N-(5-(3-(3H-Imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide244.

White solid (28.4 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 3.79(s, 2H), 7.28 (tt, J=7.04 Hz, J=1.76 Hz, 1H), 7.32-7.42 (m, 4H),7.47-7.55 (m, 1H), 7.87 (dd, J=8.76 Hz, J=1.48 Hz, 1H), 7.91 (d, J=9.00Hz, 1H), 8.29 (d, J=8.78 Hz, 1H), 8.53 (d, J=5.27 Hz, 1H), 8.62 (s, 1H),8.75 (s, 1H), 8.83 (s, 1H), 9.01 (s, 1H), 11.05 (brs, 1H), 14.29 (brs,1H); ESIMS found for C₂₆H₁₉N₇O m/z 446.2 (M+1).

1-(5-(3-(3H-Imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine247.

Beige solid (11.1 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 2.23(s, 6H), 3.56 (s, 2H), 7.27 (dd, J=5 Hz, J=7.5 Hz, 1H), 7.78-7.96 (m,3H), 8.04 (s, 1H), 8.39 (brs, 1H), 8.51 (s, 1H), 8.75 (s, 1H), 8.86 (s,1H), 13.69 (brs, 1H), 13.89 (brs, 1H); ESIMS found for C₂₁H₁₉N₇ m/z369.7 (M+1).

N-(5-(3-(3H-Imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide250.

White solid (47.7 mg, 0.11 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.06(s, 9H), 2.38 (s, 2H), 7.70 (dd, J=8.03, 5.77 Hz, 1H), 7.91 (dd, J=8.80Hz, J=1.76 Hz, 1H), 7.98 (d, J=9.28 Hz, 1H), 8.52 (dd, J=8.03, 1.00 Hz,1H), 8.64 (dd, J=5.65, 1.13 Hz, 1H), 8.76 (d, J=0.75 Hz, 1H), 8.89 (t,J=2.01 Hz, 1H), 9.00 (d, J=1.76 Hz, 1H), 9.28 (d, J=2.01 Hz, 1H), 11.37(s, 1H), 14.68 (brs, 1H); ESIMS found for C₂₄H₂₃N₇O m/z 426.3 (M+1).

N-(5-(3-(3H-Imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide 256.

White solid (63.1 mg, 0.14 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.15-1.39 (m, 4H), 1.40-1.53 (m, 2H), 1.64-1.72 (m, 1H), 1.76-1.84 (m,2H), 1.86-1.94 (m, 2H), 7.43-7.52 (m, 1H), 7.88 (dd, J=8.80 Hz, J=1.52Hz, 1H), 7.92 (d, J=8.28 Hz, 1H), 8.23-8.28 (m, 1H), 8.52 (d, J=5.52 Hz,1H), 8.64 (s, 1H), 8.77 (s, 1H), 8.83 (d, J=1.51 Hz, 1H), 9.03 (d,J=1.25 Hz, 1H), 10.62 (brs, 1H); ESIMS found for C₂₅H₂₃N₇O m/z 438.2(M+1).

2-(5-(4-Methylpyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine265.

White solid (65.9 mg, 0.16 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.65(s, 3H), 7.67-7.73 (m, 2H), 7.77 (dd, J=4.89, 2.89 Hz, 1H), 7.90 (d,J=8.78 Hz, 1H), 8.13 (d, J=6.02 Hz, 1H), 8.18 (d, J=4.52 Hz, 1H), 8.40(d, J=5.02 Hz, 1H), 8.69 (s, 1H), 8.83-8.89 (m, 2H), 9.02 (s, 1H), 14.23(brs, 1H); ESIMS found for C₂₃H₁₆N₆S m/z 409.1 (M+1).

N-(5-(3-(7-(Thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide 268.

White solid (80.1 mg, 0.16 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.30(s, 9H), 7.66 (d, J=5.27 Hz, 1H), 7.74 (dd, J=5.02, 3.01 Hz, 1H),7.82-7.89 (m, 2H), 8.25 (d, J=5.15 Hz, 1H), 8.35 (d, J=5.14 Hz, 1H),8.60 (s, 1H), 8.70 (d, J=1.88 Hz, 1H), 8.88-8.96 (m, 3H), 9.60 (s, 1H),13.89 (brs, 2H); ESIMS found for C₂₇H₂₃N₇OS m/z 494.1 (M+1).

N-(5-(3-(7-(Thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide 269.

White solid (66.8 mg, 0.14 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.18(d, J=6.78 Hz, 6H), 2.70 (spt, J=6.88 Hz, 1H), 7.66 (d, J=5.02 Hz, 1H),7.75 (dd, J=4.89, 2.89 Hz, 1H), 7.81-7.89 (m, 2H), 8.26 (d, J=4.02 Hz,1H), 8.35 (d, J=5.02 Hz, 1H), 8.62 (brs, 1H), 8.69 (d, J=1.38 Hz, 1H),8.76 (s, 1H), 8.87-8.94 (m, 2H), 10.25 (s, 1H), 13.77 (brs, 2H); ESIMSfound for C₂₆H₂₁N₇OS m/z 480.1 (M+1).

2-Phenyl-N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide270.

White solid (11.1 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ pp 3.85(s, 2H), 7.25-7.31 (m, 1H), 7.36 (t, J=7.40 Hz, 2H), 7.40-7.45 (m, 2H),7.69-7.75 (m, 2H), 7.86-7.94 (m, 2H), 8.21 (d, J=3.89 Hz, 1H), 8.40 (d,J=5.40 Hz, 1H), 8.87 (d, J=1.63 Hz, 1H), 8.90 (s, 1H), 8.96 (d, J=4.89Hz, 2H), 9.09 (d, J=1.13 Hz, 1H), 11.46 (s, 1H), 14.19 (brs, 1H); ESIMSfound for C₃₀H₂₁N₇OS m/z 528.1 (M+1).

N-(5-(3-(7-(Thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide271.

White solid (59.8 mg, 0.12 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm7.59-7.65 (m, 2H), 7.67-7.78 (m, 3H), 7.92-8.01 (m, 2H), 8.14 (d, J=1.26Hz, 1H), 8.16 (s, 1H), 8.19 (d, J=5.27 Hz, 1H), 8.41 (d, J=5.27 Hz, 1H),8.94 (d, J=1.51 Hz, 1H), 8.99 (s, 1H), 9.08 (d, J=1.51 Hz, 1H), 9.23 (s,1H), 9.35 (d, J=1.76 Hz, 1H), 11.30 (s, 1H), 14.23 (brs, 1H); ESIMSfound for C₂₉H₁₉N₇OS m/z 514.1 (M+1).

N-(5-(3-(7-(Thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide277.

White solid (7.6 mg, 0.02 mmol). ¹H NMR (CD₃OD, 400 MHz) δ ppm 1.07 (t,J=7.40 Hz, 3H), 1.82 (q, J=7.28 Hz, 2H), 2.54 (t, J=7.40 Hz, 3H), 7.81(dd, J=5.14, 2.89 Hz, 1H), 7.92 (d, J=6.28 Hz, 1H), 7.93-7.98 (m, 3H),8.52-8.57 (m, 1H), 8.54-8.54 (m, 1H), 8.61-8.68 (m, 1H), 8.95 (d, J=3.26Hz, 2H), 9.00 (s, 1H), 9.24 (d, J=1.76 Hz, 1H); ESIMS found forC₂₆H₂₁N₇OS m/z 480.1 (M+1).

N-(5-(3-(7-(Thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide 279.

White solid (25.2 mg, 0.05 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm0.90-0.98 (m, 4H), 1.89-1.98 (m, 1H), 7.71 (d, J=5.40 Hz, 1H), 7.78 (dd,J=4.89, 3.14 Hz, 1H), 7.87-7.94 (m, 2H), 8.21 (d, J=4.52 Hz, 1H), 8.40(d, J=4.89 Hz, 1H), 8.86 (brs, 1H), 8.90 (d, J=2.51 Hz, 1H), 8.93 (s,1H), 8.95 (brs, 1H), 9.02 (brs, 1H), 11.24 (brs, 1H), 14.12 (brs, 1H);ESIMS found for C₂₆H₁₉N₇OS m/z 478.1 (M+1).

N-(5-(3-(7-(Thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide 281.

White solid (18.0 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.53-1.64 (m, 2H), 1.65-1.75 (m, 2H), 1.75-1.88 (m, 2H), 1.90-2.01 (m,2H), 2.99 (quin, J=7.91 Hz, 1H), 7.73 (d, J=5.40 Hz, 1H), 7.82 (dd,J=4.83, 2.95 Hz, 1H), 7.88-7.98 (m, 2H), 8.20 (d, J=4.52 Hz, 1H), 8.42(d, J=5.14 Hz, 1H), 8.89 (brs, 1H), 8.92 (s, 1H), 9.00 (s, 1H), 9.03(brs, 1H), 9.18 (s, 1H), 11.29 (brs, 1H), 14.28 (brs, 1H); ESIMS foundfor C₂₈H₂₃N₇OS m/z 506.1 (M+1).

N-Benzyl-1-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine283.

White solid (29.6 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm4.26-4.33 (m, 2H), 4.47 (d, J=5.02 Hz, 2H), 7.38-7.48 (m, 3H), 7.62 (dd,J=7.65, 1.63 Hz, 2H), 7.73 (d, J=5.52 Hz, 1H), 7.81 (dd, J=5.14, 2.89Hz, 1H), 7.90-7.95 (m, 1H), 8.02 (dd, J=8.66, 1.63 Hz, 1H), 8.19-8.25(m, 1H), 8.42 (d, J=5.02 Hz, 1H), 8.91-9.01 (m, 4H), 9.28 (d, J=0.75 Hz,1H), 10.13 (brs, 2H), 14.24 (brs, 1H); ESIMS found for C₃₀H₂₃N₇S m/z514.2 (M+1).

N-((5-(3-(7-(Furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine292.

White solid (16.7 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.29(t, J=7.28 Hz, 3H), 3.08 (quin, J=6.28 Hz, 2H), 4.38 (t, J=5.27 Hz, 2H),7.47 (d, J=1.00 Hz, 1H), 7.63 (d, J=4.52 Hz, 1H), 7.87-8.03 (m, 3H),8.39 (d, J=4.52 Hz, 1H), 8.77 (d, J=1.25 Hz, 1H), 8.88 (s, 1H), 8.96 (s,1H), 9.04 (s, 1H), 9.23 (s, 1H), 9.41-9.53 (m, 2H), 14.15 (brs, 1H);ESIMS found for C₂₅H₂₁N₇O m/z 436.1 (M+1).

N-(5-(3-(7-(Furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide 295.

White solid (34.7 mg, 0.07 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.19(d, J=6.78 Hz, 6H), 2.77 (spt, J=6.87 Hz, 1H), 7.47 (d, J=1.25 Hz, 1H),7.66 (d, J=5.27 Hz, 1H), 7.88-7.97 (m, 3H), 8.41 (d, J=5.27 Hz, 1H),8.90 (s, 1H), 8.99 (s, 2H), 9.03 (s, 1H), 9.17 (s, 1H), 11.14 (brs, 1H),14.26 (brs, 1H); ESIMS found for C₂₆H₂₁N₇O₂ m/z 464.1 (M+1).

5-(3-(7-(Furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N-isopropylpyridin-3-amine298.

White solid (41.2 mg, 0.10 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.25(d, J=6.27 Hz, 6H), 3.85-3.95 (m, 1H), 7.48 (d, J=1.25 Hz, 1H), 7.67 (d,J=5.27 Hz, 1H), 7.90 (s, 2H), 7.96 (t, J=1.63 Hz, 1H), 7.98 (s, 1H),8.11 (d, J=2.01 Hz, 1H), 8.42 (d, J=4.77 Hz, 1H), 8.44 (s, 1H), 8.87 (s,1H), 9.02 (s, 1H), 14.28 (brs, 1H); ESIMS found for C₂₅H₂₁N₇O m/z 436.2(M+1).

N-(5-(3-(7-(Furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide 304.

White solid (10.6 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.93(t, J=7.28 Hz, 3H), 1.38 (dq, J=14.84, 7.27 Hz, 3H), 1.65 (quin, J=7.47Hz, 2H), 7.49 (d, J=1.00 Hz, 1H), 7.66 (d, J=4.52 Hz, 1H), 7.87-7.97 (m,3H), 8.41 (d, J=5.02 Hz, 1H), 8.90 (s, 1H), 8.91 (brs, 1H), 8.99 (s,1H), 9.03 (s, 1H), 9.13 (s, 1H), 11.11 (brs, 1H), 14.24 (brs, 1H); ESIMSfound for C₂₇H₂₃N₇O₂ m/z 478.2 (M+1).

N-(5-(3-(7-(Furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide 306.

White solid (11.0 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.79-1.91 (m, 1H), 1.92-2.07 (m, 1H), 2.15-2.26 (m, 2H), 2.26-2.37 (m,2H), 3.42 (quin, J=8.25 Hz, 1H), 7.48 (d, J=1.13 Hz, 1H), 7.68 (d,J=4.77 Hz, 1H), 7.87-7.97 (m, 3H), 8.42 (d, J=5.02 Hz, 1H), 8.88 (s,1H), 8.99 (s, 1H), 9.03 (s, 2H), 9.18 (brs, 1H), 11.14 (brs, 1H), 14.34(brs, 1H); ESIMS found for C₂₇H₂₁N₇O₂ m/z 476.1 (M+1).

1-Cyclopentyl-N-((5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine310.

White solid (69.3 mg, 0.14 mmol). ¹H NMR (CD₃OD 400 MHz) δ ppm 1.33-1.45(m, 2H), 1.61-1.81 (m, 4H), 1.93-2.04 (m, 2H), 2.33-2.44 (m, 1H), 3.25(d, J=7.28 Hz, 2H), 4.63 (brs, 2H), 7.26-7.32 (m, 1H), 7.82-7.96 (m,3H), 8.00-8.07 (m, 1H), 8.47-8.54 (m, 1H), 8.79-8.85 (m, 1H), 8.97-9.04(m, 1H), 9.07 (brs, 1H), 9.21-9.27 (m, 1H), 9.34 (s, 1H); ESIMS foundfor C₂₉H₂₇N₇O m/z 490.1 (M+1).

N-(5-(3-(7-(Thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide 313.

White solid (6.5 mg, 0.01 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.16(t, J=7.40 Hz, 3H), 3.36-3.50 (m, 2H), 7.34 (t, J=4.14 Hz, 1H), 7.69 (d,J=4.77 Hz, 1H), 7.87-7.96 (m, 3H), 8.36 (d, J=2.76 Hz, 2H), 8.97 (brs,1H), 8.99 (brs, 1H), 9.09 (s, 1H), 9.12 (brs, 1H), 11.17 (s, 1H), 14.19(brs, 1H); ESIMS found for C₂₅H₁₉N₇OS m/z 466.1 (M+1).

N,N-Dimethyl-5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine319.

White solid (15.0 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 3.21(s, 6H), 7.32-7.38 (m, 1H), 7.69 (d, J=5.27 Hz, 1H), 7.90 (d, J=8.78 Hz,1H), 7.94-8.01 (m, 1H), 8.04 (dd, J=8.28 Hz, J=0.76 Hz, 2H), 8.27 (d,J=2.76 Hz, 1H), 8.32-8.38 (m, 2H), 8.51 (s, 1H), 9.12 (s, 1H), 14.14(brs, 1H); ESIMS found for C₂₄H₁₉N₇S m/z 438.3 (M+1).

N-(5-(3-(7-(Thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide 320.

White solid (30.8 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.32(s, 9H), 7.33 (dd, J=4.89, 3.76 Hz, 1H), 7.69 (d, J=5.27 Hz, 1H),7.89-7.96 (m, 3H), 8.35 (d, J=5.40 Hz, 1H), 8.38 (d, J=3.01 Hz, 1H),9.01 (d, J=1.38 Hz, 1H), 9.10 (s, 1H), 9.24 (s, 1H), 9.36 (d, J=1.51 Hz,1H), 10.56 (s, 1H), 14.24 (brs, 1H); ESIMS found for C₂₇H₂₃N₇OS m/z 494.(M+1).

N-(5-(3-(7-(Thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide 321.

White solid (18.3 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.20(d, J=6.78 Hz, 6H), 2.79 (spt, J=6.40 Hz, 1H), 7.31-7.36 (m, 1H),7.66-7.71 (m, 1H), 7.88-7.96 (m, 3H), 8.35 (d, J=5.40 Hz, 1H), 8.37 (d,J=3.01 Hz, 1H), 8.98 (s, 1H), 9.00-9.07 (m, 1H), 9.08 (s, 1H), 9.14-9.22(m, 1H), 11.15 (brs, 1H), 14.21 (brs, 1H); ESIMS found for C₂₆H₂₁N₇OSm/z 480.1 (M+1).

N,N-Dimethyl-1-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine325.

White solid (16.5 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.81(d, J=4.27 Hz, 6H), 4.57 (d, J=3.76 Hz, 2H), 7.33-7.39 (m, 1H), 7.71 (d,J=5.27 Hz, 1H), 7.93 (d, J=8.78 Hz, 1H), 7.99 (d, J=4.77 Hz, 1H),8.03-8.10 (m, 1H), 8.36 (d, J=5.52 Hz, 1H), 8.39 (dd, J=3.76 Hz, J=0.76Hz, 1H), 8.97-9.09 (m, 2H), 9.12 (s, 1H), 9.31 (brs, 1H), 11.51 (brs,1H), 14.24 (brs, 1H); ESIMS found for C₂₅H₂₁N₇S m/z 452.2 (M+1).

N-(5-(3-(7-(Thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide 331.

White solid (32.6 mg, 0.07 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm0.79-0.95 (m, 4H), 1.88-2.03 (m, 1H), 7.26-7.32 (m, 1H), 7.64 (d, J=5.02Hz, 1H), 7.75 (d, J=5.02 Hz, 1H), 7.84 (s, 2H), 8.32 (d, J=5.27 Hz, 1H),8.34 (d, J=3.01 Hz, 1H), 8.62-8.65 (m, 1H), 8.70 (s, 1H), 8.75 (d,J=1.51 Hz, 1H), 9.04 (s, 1H), 10.81 (s, 1H), 13.86 (brs, 1H), 14.03(brs, 1H); ESIMS found for C₂₆H₁₉N₇OS m/478.1 (M+1).

N-(5-(3-(7-(Thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide 333.

White solid (31.0 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.56-1.66 (m, 2H), 1.66-1.75 (m, 2H), 1.76-1.86 (m, 2H), 1.90-2.00 (m,2H), 2.98 (quin, J=7.87 Hz, 1H), 7.31-7.37 (m, 1H), 7.68 (d, J=5.40 Hz,1H), 7.87-7.96 (m, 3H), 8.35 (d, J=5.40 Hz, 1H), 8.37 (d, J=3.64 Hz,1H), 8.98 (s, 1H), 9.04 (brs, 1H), 9.08 (s, 1H), 9.18 (s, 1H), 11.26(brs, 1H), 14.21 (brs, 1H); ESIMS found for C₂₈H₂₃N₇OS m/z 506.1 (M+1).

2-(5-(5-((3,3-Difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine337.

White solid (11.3 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm2.56-2.68 (m, 2H), 4.58-4.71 (m, 2H), 7.35 (d, J=4.27 Hz, 1H), 7.70 (dd,J=4.27, 3.01 Hz, 1H), 7.89-7.99 (m, 2H), 7.99-8.08 (m, 1H), 8.36 (d,J=5.02 Hz, 1H), 8.39 (d, J=3.26 Hz, 1H), 8.89-8.97 (m, 1H), 8.97-9.05(m, 1H), 9.14 (s, 1H), 9.24-9.32 (m, 1H), 14.15 (brs, 1H); ESIMS foundfor C₂₇H₂₁F₂N₇S m/z 514.2 (M+1).

N-(5-(3-(7-(5-Fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide340.

White solid (6.9 mg, 0.01 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.97(d, J=6.65 Hz, 6H), 2.10-2.16 (m, 1H), 2.30 (d, J=7.03 Hz, 2H),6.91-6.95 (m, 1H), 7.69 (d, J=4.77 Hz, 1H), 7.88 (s, 2H), 7.95-8.01 (m,1H), 8.32 (d, J=5.27 Hz, 1H), 8.73 (s, 1H), 8.82 (s, 1H), 8.91 (s, 1H),9.05 (s, 1H), 10.53 (brs, 1H), 14.01 (s, 1H); ESIMS found forC₂₇H₂₂FN₇OS m/z 512.2 (M+1).

N-(5-(3-(7-(5-Fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide346.

White solid (12.8 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.29(s, 9H), 6.94 (dd, J=4.08, 1.57 Hz, 1H), 7.67 (d, J=5.40 Hz, 1H),7.87-7.97 (m, 2H), 8.02 (t, J=3.95 Hz, 1H), 8.31 (d, J=5.40 Hz, 1H),9.02 (s, 2H), 9.32 (s, 1H), 9.39 (d, J=1.51 Hz, 1H), 10.59 (s, 1H),14.30 (brs, 1H); ESIMS found for C₂₇H₂₂FN₇OS m/z 512.2 (M+1).

7-(5-Fluorothiophen-2-yl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine352.

White solid (58.6 mg, 0.12 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.86-1.96 (m, 2H), 2.00-2.10 (m, 2H), 3.11-3.21 (m, 2H), 3.40-3.49 (m,2H), 4.54 (d, J=5.40 Hz, 2H), 6.94-6.98 (m, 1H), 7.71 (d, J=5.27 Hz,1H), 7.89 (d, J=8.53 Hz, 1H), 7.97-8.03 (m, 2H), 8.33 (d, J=5.40 Hz,1H), 8.68 (s, 1H), 8.89 (s, 1H), 9.08 (s, 1H), 9.18 (s, 1H), 11.20 (s,1H), 14.08 (brs, 1H); ESIMS found for C₂₇H₂₂FN₇S m/z 496.1 (M+1).

N-(5-(3-(7-(5-Fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide358.

White solid (6.7 mg, 0.01 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.78-1.90 (m, 1H), 1.94-2.06 (m, 1H), 2.13-2.35 (m, 4H), 3.33-3.44 (m,1H), 6.95 (d, J=2.26 Hz, 1H), 7.69 (d, J=5.27 Hz, 1H), 7.88-7.97 (m,2H), 8.01 (t, J=3.64 Hz, 1H), 8.33 (d, J=5.27 Hz, 1H), 8.99 (s, 1H),9.05 (brs, 1H), 9.07 (s, 1H), 9.15 (s, 1H), 10.97 (s, 1H), 14.19 (brs,1H); ESIMS found for C₂₇H₂₀FN₇OS m/z 510.1 (M+1).

5-(3-(7-(5-Methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine367.

White solid (11.6 mg, 0.03 mmol). ¹H NMR (CD₃OD, 400 MHz) δ ppm 2.66 (s,3H), 2.68 (s, 2H), 7.14 (dd. J=4.04 Hz, J=1.04 Hz, 1H), 7.82 (d, J=6.27Hz, 1H), 7.85 (dd, J=8.76 Hz, J=1.48 Hz, 1H), 7.88 (d, J=8.76 Hz, 1H),8.04-8.08 (m, 2H), 8.16 (d, J=3.51 Hz, 1H), 8.34 (s, 1H), 8.38 (d,J=6.52 Hz, 1H), 8.91 (s, 1H); ESIMS found for C₂₃H₁₇N₇S m/z 424.0 (M+1).

N-(5-(3-(7-(5-Methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide372.

White solid (56.6 mg, 0.11 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.30(s, 9H), 2.52 (s, 3H), 7.01 (d, J=3.01 Hz, 1H), 7.58 (d, J=5.27 Hz, 1H),7.87-7.95 (m, 2H), 8.22 (d, J=3.64 Hz, 1H), 8.31 (d, J=5.40 Hz, 1H),9.00 (d, J=1.51 Hz, 1H), 9.05 (s, 1H), 9.09 (s, 1H), 9.31 (d, J=1.63 Hz,1H), 10.31 (s, 1H), 14.15 (brs, 1H); ESIMS found for C₂₈H₂₅N₇OS m/z508.1 (M+1).

N-(5-(3-(7-(5-Methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide373.

White solid (10.3 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.17(d, J=7.03 Hz, 6H), 2.54 (s, 3H), 2.69-2.77 (m, 1H), 7.01 (dd, J=3.64,1.13 Hz, 1H), 7.60 (d, J=5.27 Hz, 1H), 7.84-7.93 (m, 2H), 8.16 (d,J=3.76 Hz, 1H), 8.30 (d, J=5.27 Hz, 1H), 8.76 (s, 1H), 8.92 (d, J=1.76Hz, 1H), 9.08 (d, J=1.76 Hz, 1H), 9.11 (s, 1H), 10.77 (brs, 1H), 14.07(brs, 1H); ESIMS found for C₂₇H₂₃N₇OS m/z 494.2 (M+1).

7-(5-Methylthiophen-2-yl)-2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine379.

White solid (18.9 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.29-1.44 (m, 2H), 1.44-1.64 (m, 4H), 2.30-2.49 (m, 4H), 2.61 (s, 3H),3.54-3.69 (m, 2H), 6.99 (dd, J=3.51, 1.00 Hz, 1H), 7.59 (d, J=5.27 Hz,1H), 7.82-7.87 (m, 1H), 7.88-7.95 (m, 1H), 8.02-8.16 (m, 2H), 8.29 (d,J=5.27 Hz, 1H), 8.52-8.63 (m, 1H), 9.00-9.11 (m, 1H), 9.16-9.22 (m, 1H),13.83 (brs, 1H), 14.01 (s, 1H); ESIMS found for C₂₉H₂₇N₇S m/z 506.3(M+1).

N-(5-(3-(7-(5-Methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide385.

White solid (21.9 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.55-1.65 (m, 2H), 1.65-1.74 (m, 2H), 1.74-1.84 (m, 2H), 1.87-1.99 (m,2H), 2.53 (s, 3H), 2.86-2.98 (m, 1H), 7.01 (dd, J=3.64, 0.88 Hz, 1H),7.60 (d, J=5.27 Hz, 1H), 7.84-7.95 (m, 2H), 8.17 (d, J=3.51 Hz, 1H),8.31 (d, J=5.27 Hz, 1H), 8.82 (s, 1H), 8.95 (d, J=1.51 Hz, 1H), 9.10 (s,1H), 9.13 (d, J=1.76 Hz, 1H), 10.94 (brs, 1H), 14.11 (brs, 1H); ESIMSfound for C₂₉H₂₅N₇OS m/z 520.1 (M+1).

N-(3-fluoro-5-(2-(5-(4-Methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide421.

White solid (12.5 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.60(s, 3H), 2.88 (s, 3H), 4.23 (d, J=6.02 Hz, 2H), 7.31 (d, J=9.04 Hz, 1H),7.64-7.69 (m, 2H), 7.74 (t, J=6.02 Hz, 1H), 7.90 (d, J=9.03 Hz, 1H),8.12 (d, J=6.02 Hz, 2H), 8.29-8.38 (m, 1H), 8.46 (d, J=5.02 Hz, 1H),8.66 (s, 1H), 8.86 (d, J=6.27 Hz, 1H), 8.99 (s, 1H), 14.22 (brs, 1H);ESIMS found for C₂₇H₂₂FN₇O₂S m/z 528.3 (M+1).

N-(5-(3-(7-(3-Fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide427.

White solid (23.1 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.90(s, 3H), 4.28 (d, J=6.27 Hz, 2H), 7.14 (dd, J=7.15, 1.63 Hz, 1H),7.57-7.64 (m, 2H), 7.65-7.70 (m, 2H), 7.73 (t, J=6.53 Hz, 1H), 7.90 (d,J=1.00 Hz, 2H), 8.02-8.07 (m, 2H), 8.13-8.20 (m, 1H), 8.46 (d, J=5.02Hz, 1H), 8.52-8.64 (m, 1H), 8.71 (brs, 1H), 8.85 (d, J=1.76 Hz, 1H),8.95 (s, 1H), 9.13 (d, J=2.01 Hz, 1H), 10.72 (s, 1H), 14.03 (s, 1H);ESIMS found for C₃₃H₂₅FN₈O₃S m/z 633.1 (M+1).

N-(5-(3-(7-(3-Fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide433.

White solid (6.4 mg, 0.01 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.97(t, J=7.40 Hz, 3H), 1.67 (sxt, J=7.28 Hz, 3H), 2.43 (t, J=7.28 Hz, 2H),2.89 (s, 3H), 4.30 (d, J=6.02 Hz, 2H), 7.28-7.37 (m, 1H), 7.70 (d,J=5.27 Hz, 1H), 7.71-7.79 (m, 2H), 7.87 (dd, J=8.76 Hz, J=1.76 Hz, 1H),7.92 (d, J=8.28 Hz, 1H), 8.11-8.22 (m, 1H), 8.48 (d, J=5.27 Hz, 1H),8.70 (s, 1H), 8.90 (s, 1H), 8.93 (d, J=1.51 Hz, 1H), 9.10 (d, J=1.76 Hz,1H), 10.79 (brs, 1H), 14.15 (brs, 1H); ESIMS found for C₃₀H₂₇FN₈O₃S m/z599.2 (M+1).

N-(3-(2-(5-(5-((Benzylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide439.

White solid (50.1 mg, 0.08 mmol). ¹H NMR (CD₃OD, 400 MHz) δ ppm 3.01 (s,3H), 4.46 (s, 2H), 4.48 (s, 2H), 4.69 (s, 2H), 7.44-7.53 (m, 4H), 7.65(dd, J=7.53, 2.01 Hz, 2H), 7.73-7.79 (m, 1H), 7.85 (s, 1H), 7.87 (d,J=6.27 Hz, 1H), 7.95 (dd, J=8.80 Hz, J=0.72 Hz, 1H), 8.03 (dd, J=8.80Hz, J=1.76 Hz, 1H), 8.66 (d, J=6.27 Hz, 1H), 9.04 (d, J=1.51 Hz, 1H),9.07 (d, J=0.75 Hz, 1H), 9.19 (s, 1H), 9.35 (d, J=1.76 Hz, 1H); ESIMSfound for C₃₄H₂₉FN₈O₂S m/z 633.3 (M+1).

N-(3-Fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide442.

White solid (17.3 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.94(s, 3H), 4.34 (d, J=6.40 Hz, 2H), 7.35 (d, J=9.54 Hz, 1H), 7.68 (d,J=5.27 Hz, 1H), 7.76 (t, J=6.34 Hz, 1H), 7.88 (d, J=8.56 Hz, 1H), 7.96(dd, J=8.64 Hz, J=1.60 Hz, 1H), 8.21 (s, 1H), 8.44 (d, J=5.14 Hz, 1H),8.57 (d, J=10.29 Hz, 1H), 8.95 (d, J=0.63 Hz, 1H), 9.24 (s, 1H), 9.26(s, 2H), 13.98 (brs, 1H), 14.00 (s, 1H); ESIMS found for C₂₅H₁₉FN₈O₂Sm/z 515.0 (M+1).

N¹-(3-(2-(5-(5-((Ethylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine448.

White solid (13.9 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.29(t, J=7.28 Hz, 3H), 2.81 (s, 3H), 2.82 (s, 3H), 3.00-3.11 (m, 3H),3.23-3.31 (m, 2H), 3.57 (t, J=6.40 Hz, 2H), 4.39 (t, J=5.52 Hz, 4H),6.68 (d, J=11.80 Hz, 1H), 7.33 (d, J=1.25 Hz, 1H), 7.44-7.55 (m, 1H),7.65 (d, J=5.52 Hz, 1H), 7.94 (d, J=8.80 Hz, 1H), 8.02 (dd, J=8.80 Hz,J=1.52 Hz, 1H), 8.50 (d, J=5.02 Hz, 1H), 8.88 (s, 1H), 8.93 (s, 1H),8.99 (s, 1H), 9.26 (d, J=2.01 Hz, 1H), 9.80 (brs, 2H); ESIMS found forC₃₁H₃₂FN₉ m/z 550.2 (M+1).

N¹-(3-Fluoro-5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine454.

White solid (21.9 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.21(d, J=6.27 Hz, 6H), 2.80 (s, 3H), 2.81 (s, 3H), 3.19-3.26 (m, 2H),3.50-3.57 (m, 2H), 3.79-3.89 (m, 1H), 6.60 (d, J=11.04 Hz, 1H),7.04-7.16 (m, 1H), 7.26-7.35 (m, 1H), 7.59 (d, J=5.77 Hz, 1H), 7.82-7.92(m, 3H), 8.09 (d, J=2.26 Hz, 1H), 8.38 (s, 1H), 8.42 (d, J=5.77 Hz, 1H),8.83 (s, 1H), 10.34 (brs, 2H), 14.13 (brs, 2H); ESIMS found forC₃₁H₃₂FN₉ m/z 550.3 (M+1).

N-(5-(3-(7-(3-((2-(Dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide460.

White solid (51.5 mg, 0.09 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.93(t, J=7.40 Hz, 3H), 1.37 (sxt, J=7.28 Hz, 2H), 1.63 (quin, J=7.28 Hz,2H), 2.44 (t, J=7.53 Hz, 2H), 2.82 (brs, 3H), 2.83 (brs, 3H), 3.21-3.30(m, 2H), 3.50-3.57 (m, 2H), 6.61 (d, J=11.80 Hz, 1H), 7.34-7.44 (m, 1H),7.60 (d, J=5.27 Hz, 1H), 7.84 (dd, J=9.00 Hz, J=1.28 Hz, 1H), 7.92 (d,J=8.56 Hz, 1H), 8.42-8.48 (m, 1H), 8.60 (d, J=1.25 Hz, 1H), 8.88 (s,2H), 9.00-9.05 (m, 1H), 10.09 (brs, 1H), 10.69 (brs, 1H), 14.11 (brs,1H); ESIMS found for C₃₃H₃₄FN₉O m/z 592.4 (M+1).

N¹-(3-(2-(5-(5-(((Cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine466.

White solid (54.9 mg, 0.09 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.20-1.32 (m, 2H), 1.45-1.65 (m, 4H), 1.74-1.85 (m, 2H), 2.19-2.31 (m,1H), 2.82 (brs, 3H), 2.83 (brs, 3H), 2.90-2.99 (m, 2H), 3.23-3.32 (m,2H), 3.33-3.44 (m, 2H), 4.32 (brs, 2H), 6.64 (d, J=11.04 Hz, 1H),7.39-7.47 (m, 1H), 7.58 (d, J=5.02 Hz, 1H), 7.64-7.74 (m, 1H), 7.86-7.98(m, 2H), 8.42 (d, J=5.52 Hz, 1H), 8.57 (brs, 1H), 8.83 (s, 1H), 8.93 (s,1H), 9.14 (s, 1H), 9.33-9.45 (m, 2H), 10.41 (brs, 1H), 14.09 (brs, 1H);ESIMS found for C₃₅H₃₈FN₉ m/z 604.4 (M+1).

7-(3-Fluorophenyl)-2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine1873.

Gray solid (5.0 mg, 0.01 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm1.59-1.70 (m, 2H), 1.90 (br d, J=10.70 Hz, 2H), 2.62-2.72 (m, 2H), 2.78(br t, J=11.66 Hz, 1H), 3.11 (br d, J=11.80 Hz, 2H), 7.35-7.44 (m, 2H),7.58-7.70 (m, 4H), 8.31 (br s, 1H), 8.39 (d, J=4.94 Hz, 1H), 8.50 (s,1H), 8.64 (br s, 1H), 13.62 (brs, 1H); ESIMS found for C₂₄H₂₁FN₆ m/z413.2 (M+1).

7-(3-Fluorophenyl)-2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine1874.

Brown solid (17.0 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 2.71(br s, 2H), 3.22 (br t, J=5.63 Hz, 1H), 3.63 (br s, 2H), 6.37 (br s,1H), 7.35-7.43 (m, 1H), 7.61-7.68 (m, 2H), 7.68-7.76 (m, 2H), 8.28 (brs, 1H), 8.41 (d, J=5.21 Hz, 1H), 8.64-8.76 (m, 2H), 13.78 (brs, 1H);ESIMS found for C₂₄H₁₉FN₆ m/z 411.2 (M+1).

2-(5-(1H-Pyrazol-4-yl)-1H-indazol-3-yl)-7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridine1875.

Pink solid (4.7 mg, 0.01 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm7.38-7.44 (m, 1H), 7.64-7.72 (m, 3H), 7.79 (br d, J=7.68 Hz, 1H), 7.98(br s, 1H), 8.19 (br s, 1H), 8.29 (br d, J=7.68 Hz, 1H), 8.41 (br d,J=4.94 Hz, 1H), 8.72-8.81 (m, 2H), 13.03 (br s, 1H), 13.75 (br s, 1H),13.81 (br s, 1H); ESIMS found for C₂₂H₁₄FN₇ m/z 396.2 (M+1).

7-(3-Fluorophenyl)-2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine1876.

Yellow solid (10.0 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 3.93(s, 3H), 7.38-7.45 (m, 1H), 7.65-7.76 (m, 4H), 7.90 (s, 1H), 8.14 (s,1H), 8.26 (br d, J=7.14 Hz, 1H), 8.41 (d, J=5.21 Hz, 1H), 8.76 (br s,2H), 13.77 (br s, 2H); ESIMS found for C₂₃H₁₆FN₇ m/z 410.1 (M+1).

2-(5-(1,2-Dimethyl-1H-imidazol-5-yl)-1H-indazol-3-yl)-7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridine1877.

Brown solid (9.3 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 2.41(s, 3H), 3.64 (s, 3H), 6.97 (s, 1H), 7.37 (br s, 1H), 7.56-7.68 (m, 3H),7.77 (br d, J=8.51 Hz, 1H), 8.25 (br d, J=7.14 Hz, 1H), 8.41 (br d,J=4.94 Hz, 1H), 8.52 (br d, J=10.70 Hz, 1H), 8.61 (s, 1H), 13.88 (br s,2H); ESIMS found for C₂₄H₁₈FN₇ m/z 424.1 (M+1).

1-(6-(3-(7-(3-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine1878.

Yellow solid (2.1 mg, 0.004 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 3.71(dd, J=8.23, 5.76 Hz, 2H), 3.86-3.94 (m, 1H), 4.28 (t, J=7.68 Hz, 2H),7.35-7.42 (m, 1H), 7.60-7.69 (m, 2H), 7.78 (d, J=8.78 Hz, 1H), 7.84 (s,1H), 8.20 (br d, J=8.78 Hz, 1H), 8.34 (br s, 1H), 8.40 (br d, J=4.94 Hz,1H), 8.50 (s, 2H), 9.22 (s, 1H), 13.83 (br s, 2H); ESIMS found forC₂₆H₂₀FN₉ m/z 478.2 (M+H).

2-(5-(5-(Cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridine1879.

Brown solid (35 mg, 0.062 mmol, 73.5% yield). ¹H NMR (DMSO-d₆, 500 MHz)δ ppm 1.26-1.34 (m, 1H), 1.40 (dtd, J=13.21, 10.14, 10.14, 3.29 Hz, 2H),1.47-1.58 (m, 3H), 1.68-1.78 (m, 2H), 1.95-2.04 (m, 2H), 4.57-4.66 (m,1H), 7.34 (td, J=8.37, 2.47 Hz, 1 H), 7.63 (td, J=8.03, 6.45 Hz, 1H),7.68-7.73 (m, 2H), 7.82 (d, J=8.51 Hz, 1H), 7.90 (dd, J=8.64, 1.78 Hz,1H), 8.33 (d, J=2.74 Hz, 1H), 8.39 (d, J=7.96 Hz, 1H), 8.42 (d, J=5.21Hz, 1H), 8.54 (dt, J=10.98, 2.06 Hz, 1H), 8.59 (d, J=1.92 Hz, 1H), 8.91(s, 1H), 13.91 (s, 1H), 13.93 (s, 1H); ESIMS found for C₃₀H₂₅FN₆O m/z505.2 (M+1).

7-(3-Fluorophenyl)-2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine1880.

Brown solid (14 mg, 0.026 mmol, 74.4% yield). ¹H NMR (DMSO-d₆, 500 MHz)δ ppm 1.86-1.97 (m, 2H), 2.17 (ddd, J=10.15, 7.00, 3.43 Hz, 2H), 3.11(ddd, J=12.69, 8.71, 3.57 Hz, 2H), 3.26-3.32 (m, 2H), 4.91 (tt, J=7.41,3.43 Hz, 1H), 7.38 (td, J=8.58, 2.33 Hz, 1H), 7.64 (td, J=7.96, 6.31 Hz,1H), 7.69 (br d, J=3.84 Hz, 1H), 7.78-7.86 (m, 2H), 7.90 (dd, J=8.78,1.65 Hz, 1H), 8.38 (br d, J=3.84 Hz, 1H), 8.40-8.46 (m, 2H), 8.58 (br d,J=9.33 Hz, 1H), 8.65 (d, J=1.65 Hz, 1H), 8.93 (s, 1H), 13.94 (brs, 1H);ESIMS found for C₂₉H₂₄FN₇O m/z 506.2 (M+1).

N-(5-(3-(7-(3-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide1881.

Orange solid (9.1 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm1.09-1.20 (m, 2H) 1.64 (br d, J=11.53 Hz, 2H) 1.84-1.93 (m, 1H) 2.30 (brd, J=6.86 Hz, 2H) 2.43-2.49 (m, 2H) 2.93 (br d, J=12.08 Hz, 2H) 7.30(td, J=8.44, 2.06 Hz, 1H) 7.58-7.65 (m, 1H) 7.67 (d, J=4.94 Hz, 1H)7.77-7.87 (m, 2H) 8.35 (br d, J=7.41 Hz, 1H) 8.41 (d, J=4.94 Hz, 1H)8.47-8.55 (m, 2H) 8.68 (d, J=1.65 Hz, 1H) 8.77 (d, J=1.92 Hz, 1H) 8.89(s, 1H) 10.23 (s, 1H); ESIMS found for C₃₁H₂₇FN₈O m/z 547.3 (M+1).

7-(3-Fluorophenyl)-2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine1882.

Brown solid (15 mg, 0.027 mmol, 46.4% yield). ¹H NMR (DMSO-d₆, 500 MHz)δ ppm 1.68 (dt, J=6.72, 3.22 Hz, 4H), 2.52-2.57 (m, 4H), 2.86 (t, J=5.76Hz, 2H), 4.27 (t, J=5.90 Hz, 2H), 7.35 (td, J=8.44, 2.33 Hz, 1H),7.60-7.66 (m, 1H), 7.68 (br d, J=4.39 Hz, 1H), 7.73 (t, J=2.20 Hz, 1H),7.81 (d, J=8.51 Hz, 1H), 7.91 (dd, J=8.64, 1.51 Hz, 1H), 8.34 (d, J=2.47Hz, 1H), 8.37 (br d, J=8.51 Hz, 1H), 8.42 (d, J=4.94 Hz, 1H), 8.55 (brd, J=11.25 Hz, 1H), 8.61 (d, J=1.37 Hz, 1H), 8.92 (s, 1H), 13.91 (br s,2H); ESIMS found for C₃₀H₂₆FN₇O m/z 520.3 (M+1).

2-((5-(3-(7-(3-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethanamine1883.

Yellow solid (3.5 mg, 0.008 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 2.24(s, 6H) 2.70 (t, J=5.76 Hz, 2H) 4.25 (t, J=5.76 Hz, 2H) 7.35 (td,J=8.37, 2.20 Hz, 1H) 7.63 (td, J=8.03, 6.45 Hz, 1H) 7.67 (br s, 1H)7.71-7.74 (m, 1H) 7.81 (d, J=8.51 Hz, 1H) 7.91 (dd, J=8.78, 1.65 Hz, 1H)8.34 (d, J=2.74 Hz, 1H) 8.36 (br s, 1H) 8.41 (d, J=4.94 Hz, 1H) 8.54 (brd, J=7.41 Hz, 1H) 8.61 (d, J=1.92 Hz, 1H) 8.93 (s, 1H) 13.87 (br s, 1H);ESIMS found for C₂₈H₂₄FN₇O m/z 494.3 (M+1).

7-(3-Fluorophenyl)-2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine1884.

Yellow solid (12.3 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 3.95(s, 3H) 7.37 (td, J=8.51, 1.92 Hz, 1H) 7.60-7.65 (m, 1H) 7.68 (br d,J=4.94 Hz, 1H) 7.70-7.73 (m, 1H) 7.80-7.85 (m, 1H) 7.91 (dd, J=8.78,1.65 Hz, 1H) 8.32-8.37 (m, 2H) 8.42 (d, J=4.94 Hz, 1H) 8.55 (br d,J=10.70 Hz, 1H) 8.62 (d, J=1.37 Hz, 1H) 8.92 (s, 1H) 13.91 (s, 2H);ESIMS found for C₂₅H₁₇FN₆O m/z 437.2 (M+1).

5-(3-(7-(3-Fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol1885.

Yellow solid (3.6 mg, 0.009 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm7.32-7.40 (m, 1H) 7.50 (br s, 1H) 7.59-7.72 (m, 2H) 7.81 (s, 2H) 8.19(br s, 1H) 8.41 (br d, J=4.39 Hz, 2H) 8.49 (br s, 2H) 8.89 (br s, 1H)10.10 (s, 1H) 13.88 (br s, 2H); ESIMS found for C₂₄H₁₅FN₆O m/z 423.1(M+1).

2-(5-(5-(Benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridine1886.

Light brown solid (33 mg, 0.061 mmol, 20.25% yield). ¹H NMR (DMSO-d₆,500 MHz) δ ppm 5.31 (s, 2H), 7.21 (br t, J=7.41 Hz, 1H), 7.36-7.41 (m,1H), 7.42-7.48 (m, 2H), 7.54 (d, J=7.14 Hz, 2H), 7.62 (td, J=7.96, 6.31Hz, 1H), 7.69 (br d, J=4.39 Hz, 1H), 7.80-7.86 (m, 2H), 7.92 (dd,J=8.64, 1.51 Hz, 1H), 8.38 (br d, J=7.68 Hz, 1H), 8.41-8.45 (m, 2H),8.54 (br d, J=11.25 Hz, 1H), 8.66 (d, J=1.37 Hz, 1H), 8.96 (s, 1H),13.93 (br s, 2H); ESIMS found for C₃₁H₂₁FN₆O m/z 513.2 (M+1).

2-Cyclohexyl-N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide1887.

Cream colored solid (14 mg, 0.024 mmol, 27.9% yield). ¹H NMR (DMSO-d₆,500 MHz) δ ppm 0.95-1.06 (m, 2H), 1.10-1.30 (m, 3H), 1.62 (brd, J=11.53Hz, 1H), 1.67 (brd, J=13.17 Hz, 2H), 1.74 (brd, J=11.53 Hz, 2H), 1.81(ddd, J=10.91, 7.34, 3.43 Hz, 1H), 2.28 (d, J=7.14 Hz, 2H), 7.26-7.34(m, 1H), 7.58-7.66 (m, 1H), 7.70 (brd, J=5.21 Hz, 1H), 7.78-7.88 (m,2H), 8.38 (brd, J=7.68 Hz, 1H), 8.42 (d, J=4.94 Hz, 1H), 8.50 (brs, 1H),8.54 (brd, J=10.70 Hz, 1H), 8.67 (d, J=2.20 Hz, 1H), 8.76 (brd, J=1.65Hz, 1H), 8.89 (s, 1H), 10.22 (s, 1H), 13.94 (brs, 2H); ESIMS found forC₃₂H₂₈FN₇O m/z 546.3 (M+1).

7-(3-Fluorophenyl)-2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine1888.

Cream colored solid (70.0 mg, 0.16 mmol). ESIMS found for C₂₄H₁₅FN₆ m/z407.2 (M+1).

7-(3-Fluorophenyl)-2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine1889.

Cream colored solid (10 mg, 0.023 mmol, 26.6% yield). ¹H NMR (DMSO-d₆,500 MHz) δ ppm 7.40 (br dd, J=7.00, 4.53 Hz, 2H), 7.63-7.73 (m, 2H),7.79 (d, J=8.51 Hz, 1H), 7.94 (td, J=7.75, 1.78 Hz, 1H), 8.08 (d, J=7.96Hz, 1H), 8.26-8.32 (m, 1H), 8.34 (br d, J=7.96 Hz, 1H), 8.42 (br d,J=4.94 Hz, 1H), 8.70 (br d, J=10.70 Hz, 1H), 8.74 (br d, J=4.12 Hz, 1H),9.40 (s, 1H), 13.90 (br s, 2H); ESIMS found for C₂₄H₁₅FN₆ m/z 407.1(M+1).

7-(3-Fluorophenyl)-2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine1890.

Brick red colored solid (5 mg, 0.012 mmol, 4.59% yield). ¹H NMR(DMSO-d₆, 500 MHz) δ ppm 7.36-7.45 (m, 1H), 7.63-7.75 (m, 2H), 7.84 (d,J=8.78 Hz, 1H), 8.31 (dd, J=8.78, 1.65 Hz, 1H), 8.37 (br d, J=6.86 Hz,1H), 8.43 (d, J=4.94 Hz, 1H), 8.61-8.69 (m, 2H), 8.75-8.81 (m, 1H), 9.35(d, J=1.37 Hz, 1H), 9.46 (s, 1H); ESIMS found for C₂₃H₁₄FN₇ m/z 408.1(M+1).

N-(5-(3-(7-(3-(2-(Dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide2198.

Brown solid (13.7 mg, 0.023 mmol, 17.4% yield). ¹H NMR (DMSO-d₆, 500MHz) δ ppm 0.96 (d, J=6.59 Hz, 6H), 2.04-2.17 (m, 7H), 2.26 (d, J=7.14Hz, 2H), 2.42 (t, J=5.63 Hz, 2H), 4.09 (t, J=5.76 Hz, 2H), 6.92 (br d,J=10.43 Hz, 1H), 7.70 (d, J=4.94 Hz, 1H), 7.75-7.80 (m, 1H), 7.83-7.88(m, 1H), 7.98-8.05 (m, 2H), 8.36-8.44 (m, 2H), 8.64 (d, J=1.92 Hz, 1H),8.81 (d, J=2.20 Hz, 1H), 8.83 (s, 1H), 10.20 (s, 1H), 13.94 (br s, 2H);ESIMS found for C₃₃H₃₃FN₈O₂ m/z 593.3 (M+1).

N-(5-(3-(7-(3-Fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide2242.

Orange solid (9.3 mg, 0.015 mmol, 23.48% yield). ¹H NMR (DMSO-d₆, 500MHz) δ ppm 0.96 (d, J=6.59 Hz, 6H), 1.62 (br s, 4H), 2.10 (tt, J=13.45,6.72 Hz, 1H), 2.26 (d, J=7.14 Hz, 2H), 2.44 (br s, 4H), 2.63 (br s, 1H),4.13 (br s, 2H), 6.93 (br d, J=10.70 Hz, 1H), 7.70 (d, J=5.21 Hz, 1H),7.76-7.81 (m, 1H), 7.82-7.87 (m, 1H), 8.01 (br d, J=9.88 Hz, 1H), 8.04(s, 1H), 8.37-8.44 (m, 2H), 8.64 (d, J=1.92 Hz, 1H), 8.81 (d, J=1.92 Hz,1H), 8.83 (s, 1H), 10.20 (s, 1H), 13.92 (br s, 1H), 13.94 (br s, 1H);ESIMS found for C₃₅H₃₅FN₈O₂ m/z 619.3 (M+1).

N-(5-(3-(7-(3-Fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide2286.

Yellow solid (8.8 mg, 0.017 mmol, 18.25% yield). ¹H NMR (DMSO-d₆, 500MHz) δ ppm 0.97 (d, J=6.59 Hz, 6H), 2.12 (dquin, J=13.55, 6.84, 6.84,6.84, 6.84 Hz, 1H), 2.27 (d, J=7.14 Hz, 2H), 6.68 (dt, J=10.57, 1.99 Hz,1H), 7.57 (d, J=5.21 Hz, 1H), 7.71 (s, 1H), 7.76-7.88 (m, 2H), 7.99 (brd, J=10.43 Hz, 1H), 8.36-8.42 (m, 2H), 8.70 (d, J=1.92 Hz, 1H), 8.81 (d,J=1.92 Hz, 1H), 8.88 (s, 1H), 10.10 (s, 1H), 10.15 (s, 1H), 13.88 (s,1H), 13.93 (s, 1H); ESIMS found for C₂₉H₂₄FN₇O₂ m/z 522.3 (M+1).

N-(5-(3-(7-(3-Fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide2330.

Yellow solid (2.5 mg, 4.67 μmol, 3.62% yield). ¹H NMR (DMSO-d₆, 500 MHz)δ ppm 0.96 (d, J=6.59 Hz, 6H), 2.06-2.17 (m, 1H), 2.27 (d, J=7.14 Hz,2H), 3.81 (s, 3H), 6.92 (br d, J=10.70 Hz, 1H), 7.65 (br s, 1H),7.73-7.78 (m, 1H), 7.81-7.86 (m, 1H), 7.99 (br s, 1H), 8.13 (br s, 1H),8.38 (br d, J=4.94 Hz, 1H), 8.40 (s, 1H), 8.66 (d, J=1.92 Hz, 1H), 8.81(d, J=2.20 Hz, 1H), 8.86 (s, 1H), 10.21 (s, 1H), 13.87 (brs, 1H); ESIMSfound for C₃₀H₂₆FN₇O₂ m/z 536.2 (M+1).

2-(Dimethylamino)-N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide2373.

Yellow solid (4.4 mg, 0.009 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 2.33(s, 6H) 3.16 (s, 2H) 7.32 (td, J=8.44, 2.33 Hz, 1H) 7.59-7.65 (m, 1H)7.67 (br s, 1H) 7.79-7.87 (m, 2H) 8.37 (br s, 1H) 8.41 (br d, J=4.94 Hz,1H) 8.54 (t, J=2.20 Hz, 1H) 8.55-8.59 (m, 1H) 8.70 (d, J=2.20 Hz, 1H)8.90 (d, J=1.92 Hz, 2H) 10.08 (s, 1H) 13.91 (br s, 1H); ESIMS found forC₂₈H₂₃FN₈O m/z 507.2 (M+1).

Example 2

Preparation of intermediate5-(5-((dimethylamino)methyl)pyridin-3-yl)-6-fluoro-1H-indazole-3-carbaldehyde(CXXX) is depicted below in Scheme 26.

Step 1

A solution of6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole(XXII) (19.5 g, 56.3 mmol, 1.0 eq) in DME (215 mL) was added1-(5-bromopyridin-3-yl)-N,N-dimethylmethanamine (LIV) (11.5 g, 53.5mmol, 1.0 eq), Pd(PPh₃)₄ (1.95 g, 1.69 mmol, 0.03 eq), aq. Na₂CO₃ (2 M,56 mL, 2.00 eq). The mixture was stirred at 100° C. for 12 h under N₂.TLC (DCM:MeOH=10:1, Rf=0.9) showed (XXII) was consumed completely. Thesolvent was concentrated under reduce pressure. The residue wasdissolved in water (500 ml) and the aqueous phase was extracted withEtOAc (200 ml). The organic layer was washed with brine (100 mL), driedover anhydrous Na₂SO₄ and filtered. The filtrate was concentrated togive crude product which was purified by silica gel column(DCM:MeOH=30:1) to give1-(5-(6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine(CXXVI) as a brown oil (18 g, 50.8 mmol, 94.9% yield). ¹H NMR (CDCl₃,400 MHz) δ ppm 1.85-1.74 (m, 3H), 2.32-2.15 (m, 2H), 2.32 (s, 6H),2.60-2.51 (m, 1H), 3.55 (s, 2H), 3.81-3.76 (m, 1H), 4.06 (d, J=11.8 Hz,1H), 5.71 (d, J=8.8 Hz, 1H), 7.42 (d, J=11.8 Hz, 1H), 7.80 (s, 1H), 7.89(s, 1H), 8.07 (s, 1H), 8.54 (s, 1H), 8.71 (s, 1H); ESIMS foundC₂₀H₂₃FN₄O m/z 355.1 (M+1).

Step 2

To a solution of1-(5-(6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine(CXXVI) (18 g, 50.8 mmol, 1.0 eq) in DCM (50 mL) was added Et₃SiH (13.2g, 113 mmol, 2.5 eq) and TFA (51 g, 454 mmol, 10 eq). The mixture wasstirred at 25° C. for 12 h. LC/MS showed (CXXVI) was consumed. Thereaction mixture was concentrated in vacuo. The residue was diluted withTBME (200 mL). The mixture was stirred for 0.5 h at −65° C., 1 h at 25°C. The precipitate was filtered and the solid was concentrated in vacuo.The residue was dissolve in MeOH (200 mL), weakly basic resin was added.The mixture was stirred for 0.5 h, pH=7. The solid was filtered anddried in vacuo to give1-(5-(6-fluoro-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine(CXXVII) as white solid (12.0 g, 44.4 mmol, 88.3% yield). ¹H NMR (CDCl₃,400 MHz) δ ppm 2.96 (s, 6H), 4.52 (s, 2H), 7.42 (d, J=11.2 Hz, 1H), 8.02(d, J=7.2 Hz, 1H), 8.16 (s, 1H), 8.27 (s, 1H), 8.73 (s, 1H), 8.89 (s,1H); ESIMS found C₁₅H₁₅FN₄ m/z 271.1 (M+1).

Step 3

To a solution of1-(5-(6-fluoro-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine(CXXVII) (12.0 g, 44.4 mmol, 1.0 eq) in DMF (70 mL) was added KOH (7.4g, 133.2 mmol, 3.0 eq) and I₂ (16.9 g, 66.6 mmol, 1.5 eq) at 25° C. Thereaction mixture was stirred at 25° C. for 1 h. LC/MS showed (CXXVII)was consumed. The reaction mixture was quenched with 10% aqueous Na₂SO₃(100 mL) and diluted with water (300 mL) and EtOAc (200 mL). Theprecipitated solid was filtered, dried to afford product. The solutionwas separated, and the organic layer was washed with water (100 mL) andsat NaCl (100 mL), then dried over anhydrous Na₂SO₄ and concentrated toafford1-(5-(6-fluoro-3-iodo-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine(CXXVIII) as a yellow solid (10.0 g, 25.2 mmol, 56.8% yield). ¹H NMR(CDCl₃, 400 MHz) δ ppm 2.31 (s, 6H), 4.02 (d, J=7.2 Hz, 2H), 7.59-7.55(m, 2H), 7.92 (s, 1H), 8.53 (s, 1H), 8.69 (s, 1H), 13.71 (br, 1H); ESIMSfound C₁₅H₁₄FIN₄ m/z 397.1 (M+1).

Step 4

To a solution of1-(5-(6-fluoro-3-iodo-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine(CXXVIII) (1.50 g, 3.79 mmol, 1.00 eq) in THF (20 mL) was added NaH (181mg, 4.55 mmol, 1.20 eq) portion-wise at 0° C. The reaction mixture wasstirred at 20° C. for 10 min then cooled to −10° C. and i-PrMgCl (2 M,11.37 mL, 6.00 eq) was added. The reaction mixture was stirred at −10°C. for 1 h then morpholine-4-carbaldehyde (CXXIX) (3.49 g, 30.32 mmol,8.00 eq) was slowly added. The mixture was stirred at −10° C. for 20 minthen at 20° C. for 3 h. TLC (DCM:MeOH=5/1, R_(f)=0.55) show the reactionis complete. The reaction mixture was quenched with water (3 mL). Themixture was acidified with HCl (1N, 20 mL) to pH=7 and then concentratedto give crude product, which was further purified by silica gel oncolumn chromatography (DCM/MeOH=50:1→3:1) to give5-(5-((dimethylamino)methyl)pyridin-3-yl)-6-fluoro-1H-indazole-3-carbaldehyde(CXXXX) (2.9 g, 50% TLC purity) as yellow solid. The crude product wasused for step 5 without further purification. ESIMS found C₁₆H₁₅FN₄O m/z299.1 (M+1).

Step 5

Preparation of the following compounds were performed following theprocedure listed in Scheme 25, Step 2.

The following compounds were prepared in accordance with the proceduredescribed in the above Example 2.

1-(5-(7-fluoro-3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine481.

White solid (10.1 mg, 0.02 mmol). ESIMS found for C₂₇H₂₁F₂N₇ m/z 482.2(M+1).

1-(5-(7-Fluoro-3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine741.

White solid (29.6 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.81(br s, 6H), 4.60 (br s, 2H), 7.78 (br s, 3H), 8.10 (br s, 1H), 8.44 (brs, 1H), 8.73 (br d, J=7.03 Hz, 1H), 8.88 (br d, J=5.27 Hz, 2H), 9.14 (brs, 1H), 9.19 (br s, 1H), 11.78 (br s, 1H), 14.55 (br s, 1H); ESIMS foundfor C₂₅H₂₀FN₇S m/z 470.1 (M+1).

N-(3-(2-(5-(5-((Dimethylamino)methyl)pyridin-3-yl)-7-fluoro-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide897.

White solid (49.7 mg, 0.08 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.79(br s, 6H), 2.92 (s, 3H), 4.30 (br s, 2H), 4.60 (br s, 2H), 7.38 (br d,J=9.54 Hz, 1H), 7.72 (d, J=5.52 Hz, 1H), 7.78 (d, J=10.79 Hz, 1H), 7.84(br s, 1H), 8.00 (br s, 1H), 8.07 (br d, J=8.03 Hz, 1H), 8.54 (br d,J=5.27 Hz, 1H), 8.70 (d, J=7.28 Hz, 1H), 8.85 (s, 1H), 9.14 (br s, 1H),9.19 (br s, 1H), 11.64 (br s, 1H), 14.61 (br s, 1H); ESIMS found forC₂₉H₂₆F₂N₈O₂S m/z 589.2 (M+1).

1-(5-(6-Fluoro-3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine949.

White solid (11.9 mg, 0.02 mmol). ESIMS found for C₂₇H₂₁F₂N₇ m/z 482.1(M+1).

1-(5-(6-Fluoro-3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine1209.

White solid (3.6 mg, 0.008 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.81(br s, 6H), 4.49 (br s, 2H), 7.91 (d, J=7.03 Hz, 1H), 7.97 (br d,J=12.05 Hz, 1H), 8.04 (d, J=7.03 Hz, 1H), 8.45 (d, J=5.52 Hz, 1H), 8.59(d, J=5.27 Hz, 1H), 8.77 (br s, 1H), 8.86 (br d, J=6.78 Hz, 2H), 9.12(br s, 1H), 9.32 (s, 1H), 11.41 (br s, 1H), 14.83 (s, 1H); ESIMS foundfor C₂₅H₂₀FN₇S m/z 470.1 (M+1).

N-(3-(2-(5-(5-((Dimethylamino)methyl)pyridin-3-yl)-6-fluoro-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide1365.

White solid (10.2 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.80(br d, J=2.51 Hz, 6H), 2.92 (s, 3H), 4.33 (br s, 2H), 4.57 (br s, 2H),7.38 (br d, J=9.54 Hz, 1H), 7.71 (d, J=5.52 Hz, 1H), 7.83 (br s, 1H),7.99 (br d, J=12.05 Hz, 1H), 8.06 (br s, 1H), 8.25 (br d, J=7.53 Hz,1H), 8.53 (br d, J=5.52 Hz, 1H), 8.73 (s, 1H), 9.01 (br s, 1H), 9.04 (brs, 1H), 9.31 (s, 1H), 11.69 (br s, 1H), 14.84 (br s, 1H); ESIMS foundfor C₂₉H₂₆F₂N₈O₂S m/z 589.3 (M+1).

1-(5-(4-Fluoro-3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine1417.

White solid (11.1 mg, 0.2 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.79(br s, 6H), 4.55 (br s, 2H), 7.32-7.41 (m, 1H), 7.59-7.68 (m, 1H),7.71-7.78 (m, 2H), 7.84-7.92 (m, 1H), 8.14 (br d, J=7.03 Hz, 1H), 8.33(br d, J=8.53 Hz, 1H), 8.52 (br d, J=5.02 Hz, 1H), 8.84 (br s, 1H), 9.03(br s, 1H), 9.16 (br s, 1H), 11.76 (br s, 1H), 14.76 (br s, 1H); ESIMSfound for C₂₇H₂₁F₂N₇ m/z 482.1 (M+1).

1-(5-(4-Fluoro-3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine1677.

White solid (14.4 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.80(br s, 6H), 4.58 (br s, 2H), 7.74 (br d, J=8.78 Hz, 1H), 7.78-7.85 (m,3H), 7.86-7.92 (m, 2H), 8.17 (br d, J=4.77 Hz, 1H), 8.47 (br d, J=5.27Hz, 1H), 8.92 (br s, 1H), 8.94 (br s, 1H), 9.06 (s, 1H), 9.19 (s, 1H),11.83 (br s, 1H), 14.83 (br s, 1H); ESIMS found for C₂₅H₂₀FN₇S m/z 470.0(M+1).

N-(3-(2-(5-(5-((Dimethylamino)methyl)pyridin-3-yl)-4-fluoro-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide1833.

White solid (14.9 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.77(br d, J=3.31 Hz, 6H), 2.91 (s, 3H), 4.31 (d, J=2.84 Hz, 2H), 4.49 (brd, J=3.31 Hz, 2H), 7.34 (br d, J=8.82 Hz, 1H), 7.68-7.79 (m, 3H),7.81-7.88 (m, 1H), 8.22 (br s, 1H), 8.36 (d, J=7.72 Hz, 1H), 8.50 (br d,J=4.85 Hz, 1H), 8.65 (br s, 1H), 8.92 (s, 1H), 9.11 (br s, 1H), 11.42(br s, 1H), 14.55 (br s, 1H); ESIMS found for C₂₉H₂₆F₂N₈O₂S m/z 589.1(M+1).

Example 3

The screening assay for Wnt activity is described as follows. Reportercell lines can be generated by stably transducing cancer cell lines(e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells)with a lentiviral construct that includes a Wnt-responsive promoterdriving expression of the firefly luciferase gene.

SW480 colon carcinoma cells were transduced with a lentiviral vectorexpressing luciferase with a human Sp5 promoter consisting of a sequenceof eight TCF/LEF binding sites. SW480 cells stably expressing theSp5-Luc reporter gene and a hygromycin resistance gene were selected bytreatment with 150 μg/ml of hygromycin for 7 days. These stablytransduced SW480 cells were expanded in cell culture and used for allfurther screening activities. For Sp5-Luc reporter gene assays, thecells were plated at 10,000 cells/well in 96-well plates with growthmedium containing 10% fetal calf serum and incubated overnight at 37° C.and 5% CO₂. Each compound was dissolved in DMSO as a 10 mM stock instandard j-vials and used to prepare compound source plates indose-response format with 3-fold serial dilutions and a 10 mM topconcentration. Compound transfer from serially diluted source plates toassay plates containing the cells was accomplished using a pintool(Multimek 96, Beckman equipped with V&P Scientific FP1S50H pins) basedliquid handling protocol. This protocol used a slotted pin to transfer50 nl of compound from a source plate well to an assay plate wellcontaining 50 μl of cells in growth medium. The 1000-fold dilutionresulted in a final DMSO concentration of 0.1% on the cells in eachwell. Control wells received 50 nl of DMSO treatment for normalizationand calculating IC₅₀ values. The treated cells were incubated at 37° C.and 5% CO₂ for an additional forty-two hours. Following incubation, thegrowth medium was removed and 50 μl of BrightGlo luminescence reagent(Promega) was added to each well of the 96-well assay plates. The plateswere placed on an orbital shaker for 5 min and then luminescence wasquantified on the Victor3 (Perkin Elmer) plate reader. Readings werenormalized to DMSO only treated cells, and normalized activities wereutilized for IC₅₀ calculations using the dose-response log (inhibitor)vs. response-variable slope (four parameters) nonlinear regressionfeature available in GraphPad Prism 5.0 or 6.0. Table 2 shows themeasured activity for selected compounds of Formula I as describedherein.

TABLE 2 Compound IC₅₀ (μM) 1 <0.001 2 0.002 7 <0.001 9 0.003 13 0.116 190.001 21 0.0091 25 <0.001 28 0.004 34 0.019 40 4.025 46 0.002 52 0.025655 0.0018 59 0.0319 61 0.006 68 0.052 71 0.0111 73 0.013 81 0.0058 820.0035 87 0.0068 90 0.012 93 >10 101 >10 109 0.0137 114 0.054 121 0.035126 0.0307 136 1.546 141 0.0137 148 0.0081 150 0.015 154 1.462 157 0.015163 0.122 169 1.448 175 0.0993 181 2.580 184 0.0023 190 0.0074 2020.0047 211 0.0663 217 0.1734 223 3.072 229 0.2842 234 0.7948 238 0.0288239 4.100 244 0.3518 247 0.077 250 0.124 256 0.0663 265 0.0094 2680.0065 269 0.0051 270 0.0163 271 0.0084 277 0.001 279 0.0052 281 0.0098283 0.1366 292 0.04767 295 0.0051 298 0.005 304 0.006 306 0.0067 3101.274 313 0.002 319 0.0628 320 0.0088 321 0.0411 325 0.932 331 0.0347333 0.0063 337 0.015 340 0.0049 346 0.0004 352 0.0132 358 0.0069 3670.0043 372 0.0006 373 0.0064 379 0.076 385 0.0192 421 0.0061 427 0.0192433 0.003 439 0.3537 442 0.0058 448 0.203 454 0.0517 460 0.0116 4660.4419 481 0.155 741 0.9355 897 0.074 949 >10 1209 >10 1365 0.804 14170.923 1677 0.673 1833 0.773 1873 3.271 1874 >1.0 1875 0.005 1876 0.0611877 >10 1878 0.215 1879 >10 1880 1.194 1881 0.065 1882 4.135 1883 0.7531884 >10 1885 0.011 1886 >10 1887 >10 1888 >10 1889 >1.0 1890 0.039 21980.180 2242 0.440 2286 0.055 2330 0.020 2373 0.091

Example 4

The above synthesized compounds were screened using primary humanmesenchymal stem cells (hMSCs) to determine their ability to inducechondrogenesis (process by which cartilage is developed).

Human Mesenchymal Stem Cell Culture:

Primary human mesenchymal stem cells (hMSCs) were purchased from Lonza(Walkersville, Md.) and expanded in Mesenchymal Stem Cell Growth Media(Lonza). Cells between passage 3 and 6 were used for the experiments.

Compound Screening:

Each compound was dissolved in DMSO as a 10 mM stock and used to preparecompound source plates. Serial dilution (1:3, 6-point dose-responsecurves from 2700 nM to 10 nM) and compound transfer was performed usingthe ECHO 550 (Labcyte, Sunnyvale, Calif.) into 96-well clear bottomassay plates (Greiner Bio-One) with appropriate DMSO backfill for afinal DMSO concentration of 0.03%. hMSCs were plated at 20,000cells/well in 250 μL/well Incomplete Chondrogenic Induction Medium(Lonza; DMEM, dexamethasone, ascorbate, insulin-transferrin-selenium[ITS supplement], gentamycin-amphotericin [GA-1000], sodium pyruvate,proline and L-glutamine). TGF-03 (10 ng/mL) was used as a positivecontrol for differentiation while negative control wells were treatedwith 75 nL DMSO for normalization and calculating EC₅₀ values. Cellswere incubated at 37° C. and 5% CO₂ for 6 days. To image chondrogenicnodules, the cells were fixed using 4% formaldehyde (Electron MicroscopySciences), and stained with 2 μg/mL Rhodamine B (Sigma-Aldrich) and 20μM Nile Red (Sigma-Aldrich) [Johnson K., et.al, A Stem Cell-BasedApproach to Cartilage Repair, Science, (2012), 336(6082), 717-721]. Thenodules imaged (4 images per well at 4× magnification) by excitation at531 nm and emission at 625 nm and quantified using the CellInsight CX5(Thermo Scientific). Number of nodules in each well was normalized tothe average of 3 DMSO treated wells on the same plate using Excel(Microsoft Inc.). The normalized averages (fold change over DMSO) of 3replicate wells for each compound concentration were calculated. Due tosolubility limitations of some of the compounds, curve fitting wasincomplete leading to inaccurate EC₅₀ determinations.

Using TGF-β3 as a positive control, the concentration of test compoundsrequired to induce equivalent levels of chondrogenesis is reported. Inaddition, the maximum activity of each compound and the respective dosethat each compound reached maximum chondrogenesis activity is reported.Table 3 shows the activity of selected compounds as provided herein.

TABLE 3 Conc Conc Max. (nM) of (nM) of Activity as 100% Max. % TGF-β3TGF-β3 Compound activity activity activity 2 30 N/A 61.0 7 100 30 83.725 30 10 85.8 55 30 30 112.8 82 10 10 68.7 109 30 10 149.7 148 100 3089.3 184 300 N/A 60.1 277 30 30 72.6 298 30 30 84.2 346 300 30 120.1 37330 30 70.3 433 2700 2700 117.4 460 30 N/A 29.6 1875 2700 2700 174.4 1885100 N/A 52.2

Example 5

The above synthesized compounds were screened using primary humanfibroblasts (derived from IPF patients) treated with TGF-β1 to determinetheir ability to inhibit the fibrotic process.

Human Fibroblast Cell Culture:

Primary human fibroblasts derived from IPF patients (LL29 cells)[¹Xiaoqiu Liu, et.al., “Fibrotic Lung Fibroblasts Show BluntedInhibition by cAMP Due to Deficient cAMP Response Element-BindingProtein Phosphorylation”, Journal of Pharmacology and ExperimentalTherapeutics (2005), 315(2), 678-687; ²Watts, K. L., et.al., “RhoAsignaling modulates cyclin D1 expression in human lung fibroblasts;implications for idiopathic pulmonary fibrosis”, Respiratory Research(2006), 7(1), 88] were obtained from American Type Culture Collection(ATCC) and expanded in F12 medium supplemented with 15% Fetal BovineSerum and Penicillin/Streptomycin.

Compound Screening:

Each compound was dissolved in DMSO as a 10 mM stock and used to preparecompound source plates. Serial dilution (1:2, 11-point dose-responsecurves from 10 μM to 1.87 nM) and compound transfer was performed usingthe ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well clear bottomassay plates (Greiner Bio-One) with appropriate DMSO backfill for afinal DMSO concentration of 0.1%. LL29 cells were plated at 1,500cells/well in 80 μl/well F12 medium supplemented with 1% Fetal BovineSerum. One hour after addition of the cells, TGF-β1 (Peprotech; 20ng/mL) was added to the plates to induce fibrosis (ref. 1 and 2 above).Wells treated with TGF-β1 and containing DMSO were used as controls.Cells were incubated at 37° C. and 5% CO₂ for 4 days. Followingincubation for 4 days, SYTOX green nucleic acid stain (Life Technologies[Thermo Fisher Scientific]) was added to the wells at a finalconcentration of 1 uM and incubated at room temperature for 30 min.Cells were then fixed using 4% formaldehyde (Electron MicroscopySciences), washed 3 times with PBS followed by blocking andpermeabilization using 3% Bovine Serum Albumin (BSA; Sigma) and 0.3%Triton X-100 (Sigma) in PBS. Cells were then stained with antibodyspecific to α-smooth muscle actin (αSMA; Abcam) (ref. 1 and 2 above) in3% Bovine Serum Albumin (BSA; Sigma) and 0.3% Triton X-100 (Sigma) inPBS, and incubated overnight at 4° C. Cells were then washed 3 timeswith PBS, followed by incubation with Alexa Flor-647 conjugatedsecondary antibody (Life Technologies [Thermo Fisher Scientific]) andDAPI at room temperature for 1 hour. Cells were then washed 3 times withPBS and plates were sealed for imaging. αSMA staining was imaged byexcitation at 630 nm and emission at 665 nm and quantified using theCompartmental Analysis program on the CellInsight CX5 (ThermoScientific). Dead or apoptotic cells were excluded from analysis basedon positive SYTOX green staining. % of total cells positive for aSMAwere counted in each well and normalized to the average of 11 wellstreated with TGF-β1 on the same plate using Dotmatics' Studies Software.The normalized averages (fold change over untreated) of 3 replicatewells for each compound concentration were used to create dose-responsescurves and EC₅₀ values were calculated using non-linear regression curvefit in the Dotmatics' Studies Software. The EC₅₀ values are reported.

Table 4 shows the activity of selected compounds as provided herein.

TABLE 4 Inhibition of fibrosis Compound IC₅₀ (nM) 1 0.015 2 0.041 70.066 9 9.990 13 1.147 19 0.043 21 0.027 25 0.099 34 0.334 40 0.009 460.080 52 1.246 55 0.017 59 0.009 61 0.009 71 9.990 73 0.379 81 0.009 820.303 90 0.078 93 0.016 101 0.235 109 0.781 136 1.772 141 9.990 1480.085 150 0.133 154 9.990 157 0.605 163 0.009 169 0.396 175 9.990 1810.009 184 0.142 190 0.009 202 0.018 217 2.826 223 0.009 229 1.075 2340.434 238 0.013 239 0.171 247 0.184 250 2.596 256 0.401 265 0.131 2699.990 270 0.010 271 0.068 277 0.016 279 0.306 281 0.359 283 0.605 2920.009 295 0.405 298 0.102 304 0.079 306 0.527 310 9.990 313 0.027 3200.016 325 0.040 331 0.155 333 0.009 337 1.312 346 0.009 352 0.125 3670.314 372 0.009 373 0.045 379 0.405 385 0.084 421 0.045 433 >10 4390.009 448 0.701 454 0.019 460 0.111 466 1.110 1873 0.037 1874 0.317 18750.009 1876 9.990 1877 9.990 1878 9.990 1879 9.990 1880 0.417 1881 0.0711883 0.095 1884 9.990 1885 0.009 1887 9.990 1888 9.990 1889 0.018 18900.167 2373 0.233

What is claimed is:
 1. A method of treating a bone or cartilage diseaseselected from the group consisting of osteoarthritis, bone spur(osteophytes), craniosynostosis, fibrodysplasia ossificans progressive,fibrous dysplasia, giant cell tumor of bone, hip labral tear, meniscaltears, bone/osteoporotic fractures, articular cartilage (chondral)defects, degenerative disc disease, osteochondritis dissecans,osteochondroma, osteopetrosis, relapsing polychondritis, andSalter-Harris fractures in a subject, the method comprisingadministering to the subject a therapeutically effective amount of acompound of Formula I, or a pharmaceutically acceptable salt thereof:

wherein: R¹, R², and R⁴ are independently selected from the groupconsisting of H and halide; R³ is selected from the group consisting of-heteroaryl(R⁶)_(q) and -heterocyclyl(R⁷)_(h); R⁵ is selected from thegroup consisting of H, -heteroaryl(R⁸)_(q), -heterocyclyl(R⁹)_(h), and-aryl(R¹⁰)_(k); each R⁶ is one substituent attached to the heteroaryland is independently selected from the group consisting of halide,—(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R¹¹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹²)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹³)_(k),—NHC(═O)R¹⁴, —NR¹⁵R¹⁶, —(C₁₋₆ alkylene)NR¹⁷R¹⁸, and —OR²⁴; each R⁷ isone substituent attached to the heterocyclyl and is independentlyselected from the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and—CN; each R⁸ is one substituent attached to the heteroaryl and isindependently selected from the group consisting of —(C₁₋₆ alkyl),halide, —CF₃, —OCH₃, —CN, and —C(═O)R¹⁹; each R⁹ is one substituentattached to the heterocyclyl and is independently selected from thegroup consisting of —(C₁₋₆ alkyl), halide, —CF₃, —CN, and —OCH₃; eachR¹⁰ is one substituent attached to the aryl and is independentlyselected from the group consisting of —(C₁₋₆ alkyl), halide, —CF₃, —CN,—OCH₃, —(C₁₋₆ alkylene)_(p)NHSO₂R¹⁹, —NR⁵(C₁₋₆ alkylene)NR¹⁵R¹⁶, —(C₁₋₆alkylene)_(p)NR¹⁵R¹⁶, and —OR²⁷; each R¹¹ is one substituent attached tothe heterocyclyl and is independently selected from the group consistingof amino, —(C₁₋₄ alkyl), halide, —CF₃, and —CN; each R¹² is onesubstituent attached to the carbocyclyl and is independently selectedfrom the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and —CN; eachR¹³ is one substituent attached to the aryl and is independentlyselected from the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and—CN; each R¹⁴ is independently selected from the group consisting of—(C₁₋₉ alkyl), -heteroaryl(R²⁰)_(q), -aryl(R²¹)_(k), —CH₂aryl(R²¹)_(k),-carbocyclyl(R²²)_(j), —CH₂carbocyclyl(R²²)_(j), —(C₁₋₄alkylene)_(p)NR²⁵R²⁶, -heterocyclyl(R²³)_(h), and—CH₂heterocyclyl(R²³)_(h); each R¹⁵ is independently selected from thegroup consisting of H and —(C₁₋₆ alkyl); each R¹⁶ is independentlyselected from the group consisting of H, —(C₁₋₆ alkyl),—CH₂aryl(R²¹)_(k), and —CH₂carbocyclyl(R²²)_(j); each R¹⁷ isindependently selected from the group consisting of H and —(C₁₋₆ alkyl);each R¹⁸ is independently selected from the group consisting of H,—(C₁₋₆ alkyl), —CH₂aryl(R²¹)_(k), and —CH₂carbocyclyl(R²²)_(j); each R¹⁹is a —(C₁₋₆ alkyl); each R²⁰ is one substituent attached to theheteroaryl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN; each R²¹ is one substituentattached to the aryl and is independently selected from the groupconsisting of —(C₁₋₄ alkyl), halide, —CF₃, and —CN; each R²² is onesubstituent attached to the carbocyclyl and is independently selectedfrom the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and —CN; eachR²³ is one substituent attached to the heterocyclyl and is independentlyselected from the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and—CN; R²⁴ is selected from the group consisting of H, —(C₁₋₆ alkyl),—(C₁₋₄ alkylene)_(p)heterocyclyl(R²³)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R²²)_(j), —(C₁₋₄ alkylene)_(p)aryl(R²¹)_(k),and —(C₁₋₆ alkylene)_(p)NR²⁵R²⁶; each R²⁵ is independently selected fromthe group consisting of H and —(C₁₋₆ alkyl); each R²⁶ is independentlyselected from the group consisting of H and —(C₁₋₆ alkyl); R²⁷ isselected from the group consisting of H, —(C₁₋₆ alkyl), —(C₁₋₄alkylene)_(p)heterocyclyl(R²³)_(h), and —(C₁₋₆ alkylene)_(p)NR²⁵R²⁶;each p is independently 0 or 1; each q is independently 0 to 4; each his independently 0 to 10; each k is independently 0 to 5; and each j isindependently 0 to
 12. 2. The method of claim 1, wherein R³ is-heteroaryl(R⁶)_(q).
 3. The method of claim 2, wherein R³ is selectedfrom the group consisting of -pyridinyl(R⁶)_(q), -pyrimidinyl(R⁶)_(q),-pyrazolyl(R⁶)_(q), and -imidazolyl(R⁶)_(q).
 4. The method of claim 3,wherein R⁶ is selected from the group consisting of —(C₁₋₃ alkyl),—CH₂heterocyclyl(R¹¹)_(h), —NHC(═O)R¹⁴, —NR¹⁵R¹⁶, —CH₂NR¹⁷R¹⁸, and—OR²⁴.
 5. The method of claim 1, wherein R⁵ is -aryl(R¹⁰)_(k).
 6. Themethod of claim 5, wherein R⁵ is -phenyl(R¹⁰)_(k).
 7. The method ofclaim 6, wherein each R¹⁰ is independently selected from the groupconsisting of halide and is —CH₂NHSO₂R¹⁹.
 8. The method of claim 1,wherein R⁵ is -heteroaryl(R⁸)_(q).
 9. The method of claim 8, wherein R⁵is selected from the group consisting of -pyridinyl(R⁸),-imidazolyl(R⁸), -furanyl(R⁸)_(q), and -thiophenyl(R⁸)_(q).
 10. Themethod of claim 9, wherein q is 1 and R⁸ is selected from the groupconsisting of halide, —(C₁₋₃ alkyl), and —C(═O)R¹⁹.
 11. The method ofclaim 1, wherein R⁵ is -heterocyclyl(R⁹)_(h).
 12. The method of claim11, wherein R⁵ is selected from the group consisting of-piperidinyl(R⁹)_(h), -morpholinyl(R⁹)_(h), and -piperazinyl(R⁹)_(h).13. The method of claim 12, wherein h is 1 or 2 and each R⁹ isindependently selected from the group consisting of a halide an —(C₁₋₃alkyl).
 14. The method of claim 1, wherein the compound of Formula I isselected from the group consisting of:N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[1];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[2];5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[3];7-(3-fluorophenyl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[4];7-(3-fluorophenyl)-2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[5];N-((5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[6];5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N,N-dimethylpyridin-3-amine[7];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[8];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[9];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[10];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[11];5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N-isopropylpyridin-3-amine[12];1-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[13];7-(3-fluorophenyl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[14];7-(3-fluorophenyl)-2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[15];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[16];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[17];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[18];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[19];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[20];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[21];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[22];N-benzyl-1-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[23];1-cyclopentyl-N-((5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[24];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridine[25];7-(3-fluorophenyl)-2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[26];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[27];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[28];5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[29];7-(4-fluorophenyl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[30];7-(4-fluorophenyl)-2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[31];N-((5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[32];5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N,N-dimethylpyridin-3-amine[33];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[34];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[35];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[36];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[37];5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N-isopropylpyridin-3-amine[38];1-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[39];7-(4-fluorophenyl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[40];7-(4-fluorophenyl)-2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[41];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[42];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[43];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[44];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[45];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[46];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[47];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[48];N-benzyl-1-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[49];1-cyclopentyl-N-((5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[50];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridine[51];7-(4-fluorophenyl)-2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[52];N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[53];N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[54];5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[55];7-(2-fluorophenyl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[56];7-(2-fluorophenyl)-2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[57];N-((5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[58];5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N,N-dimethylpyridin-3-amine[59];N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[60];N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[61];N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[62];N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[63];5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N-isopropylpyridin-3-amine[64];1-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[65];7-(2-fluorophenyl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[66];7-(2-fluorophenyl)-2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[67];N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[68];N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[69];N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[70];N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[71];N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[72];N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[73];N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[74];N-benzyl-1-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[75];1-cyclopentyl-N-((5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[76];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridine[77];7-(2-fluorophenyl)-2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[78];N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[79];3-methyl-N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[80];5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[81];7-(pyridin-3-yl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[82];2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridine[83];N-((5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[84];N,N-dimethyl-5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[85];N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[86];N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[87];2-phenyl-N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[88];N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[89];N-isopropyl-5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[90];N,N-dimethyl-1-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[91];7-(pyridin-3-yl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[92];2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridine[93];3,3-dimethyl-N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[94];N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[95];N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[96];N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[97];N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[98];N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[99]; andN-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[100]; or a pharmaceutically acceptable salt thereof.
 15. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-benzyl-1-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[101];1-cyclopentyl-N-((5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[102];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridine[103];7-(pyridin-3-yl)-2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[104];N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[105];3-methyl-N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[106];5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[107];2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine[108];2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine[109];N-((5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[110];N,N-dimethyl-5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[111];N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[112];N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[113];2-phenyl-N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[114];N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[115];N-isopropyl-5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[116];N,N-dimethyl-1-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[117];7-(pyridin-4-yl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[118];2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine[119];3,3-dimethyl-N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[120];N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[121];N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[122];N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[123];N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[124];N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[125];N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[126];N-benzyl-1-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[127];1-cyclopentyl-N-((5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[128];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine[129];7-(pyridin-4-yl)-2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[130];N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[131];3-methyl-N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[132];5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[133];7-(pyridin-2-yl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[134];2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridine[135];N-((5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[136];N,N-dimethyl-5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[137];N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[138];N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[139];2-phenyl-N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[140];N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[141];N-isopropyl-5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[142];N,N-dimethyl-1-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[143];7-(pyridin-2-yl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[144];2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridine[145];3,3-dimethyl-N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[146];N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[147];N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[148];N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[149];N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[150];N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[151];N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[152];N-benzyl-1-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[153];1-cyclopentyl-N-((5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[154];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridine[155];7-(pyridin-2-yl)-2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[156];N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[157];3-methyl-N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[158];5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[159];7-(piperidin-1-yl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[160];2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridine[161];N-((5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[162];N,N-dimethyl-5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[163];N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[164];N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[165];2-phenyl-N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[166];N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[167];N-isopropyl-5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[168];N,N-dimethyl-1-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[169];7-(piperidin-1-yl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[170];7-(piperidin-1-yl)-2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[171];3,3-dimethyl-N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[172];N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[173];N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[174];N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[175];N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[176];N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[177];N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[178];N-benzyl-1-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[179];1-cyclopentyl-N-((5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[180];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(piperidin-1l-yl)-3H-imidazo[4,5-b]pyridine[181]; 7-(piperidin-1-yl)-2-(S-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine [182];N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[183];3-methyl-N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[184];5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[185];7-(4-methyl-1H-imidazol-1l-yl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[186]; 7-(4-methyl-1H-imidazol-1-yl)-2-(S-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[187];N-((5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[188];N,N-dimethyl-5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[189];N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[190];N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[191];N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[192];N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[193];N-isopropyl-5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[194];N,N-dimethyl-1-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[195];7-(4-methyl-1H-imidazol-1l-yl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[196];7-(4-methyl-1H-imidazol-1-yl)-2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[197];3,3-dimethyl-N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[198];N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[199]; andN-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[200]; or a pharmaceutically acceptable salt thereof.
 16. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[201];N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[202];N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[203];N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[204];N-benzyl-1-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[205];1-cyclopentyl-N-((5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[206];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridine[207];7-(4-methyl-1H-imidazol-1-yl)-2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[208];N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[209];3-methyl-N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[210];5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[211];7-(4-methylpiperazin-1-yl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[212];7-(4-methylpiperazin-1-yl)-2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[213];N-((5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[214];N,N-dimethyl-5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[215];N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[216];N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[217];N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[218];N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[219];N-isopropyl-5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[220];N,N-dimethyl-1-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[221];7-(4-methylpiperazin-1-yl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[222];7-(4-methylpiperazin-1-yl)-2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[223];3,3-dimethyl-N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[224];N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[225];N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[226];N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[227];N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[228];N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[229];N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[230];N-benzyl-1-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-H-indazol-5-yl)pyridin-3-yl)methanamine[231];1-cyclopentyl-N-((5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[232];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridine[233];7-(4-methylpiperazin-1-yl)-2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[234];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[235];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[236];5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[237]; 2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[238];2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[239];N-((5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[240];5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N,N-dimethylpyridin-3-amine[241];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[242];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[243];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[244];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[245];5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N-isopropylpyridin-3-amine[246];1-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[247];2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[248];2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[249];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[250];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[251];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[252];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[253];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[254];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[255];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[256];1-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N-benzylmethanamine[257];1-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N-(cyclopentylmethyl)methanamine[258];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[259]; 2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[260];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[261];3-methyl-N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[262];5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[263];2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[264];2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[265];N-((5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[266];N,N-dimethyl-5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[267];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[268];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[269];2-phenyl-N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[270];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[271];N-isopropyl-5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[272];N,N-dimethyl-1-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[273];2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[274];2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[275];3,3-dimethyl-N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[276];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[277];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[278];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[279];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[280];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[281];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[282];N-benzyl-1-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[283];1-cyclopentyl-N-((5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[284];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[285];2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[286];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[287];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[288];5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[289]; 7-(furan-3-yl)-2-(S-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine [290];7-(furan-3-yl)-2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[291];N-((5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[292];5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N,N-dimethylpyridin-3-amine[293];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[294];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[295];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[296];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[297];5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N-isopropylpyridin-3-amine[298];1-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[299]; and7-(furan-3-yl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[300]; or a pharmaceutically acceptable salt thereof.
 17. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:7-(furan-3-yl)-2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[301];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[302];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[303];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[304];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[305];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[306];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[307];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[308];N-benzyl-1-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[309];1-cyclopentyl-N-((5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[310];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(furan-3-yl)-3H-imidazo[4,5-b]pyridine[311];7-(furan-3-yl)-2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[312];N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[313];3-methyl-N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[314];5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[315];2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[316];2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[317];N-((5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[318];N,N-dimethyl-5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[319];N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[320];N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[321];2-phenyl-N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[322];N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[323];N-isopropyl-5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[324];N,N-dimethyl-1-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[325];2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[326];2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[327];3,3-dimethyl-N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[328];N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[329];N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[330];N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[331];N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[332];N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[333];N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[334];N-benzyl-1-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[335];1-cyclopentyl-N-((5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[336];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[337];2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[338];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[339];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[340];5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[341];7-(5-fluorothiophen-2-yl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[342];7-(5-fluorothiophen-2-yl)-2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[343];N-((5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[344];5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N,N-dimethylpyridin-3-amine[345];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[346];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[347];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[348];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[349];5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N-isopropylpyridin-3-amine[350];1-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[351];7-(5-fluorothiophen-2-yl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[352];7-(5-fluorothiophen-2-yl)-2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[353];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[354];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[355];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[356];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[357];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[358];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[359];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[360];N-benzyl-1-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[361];1-cyclopentyl-N-((5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[362];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridine[363];7-(5-fluorothiophen-2-yl)-2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[364];N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[365];3-methyl-N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[366];5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[367];7-(5-methylthiophen-2-yl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[368];2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridine[369];N-((5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[370];N,N-dimethyl-5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[371];N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[372];N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[373];N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[374];N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[375];N-isopropyl-5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[376];N,N-dimethyl-1-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[377];7-(5-methylthiophen-2-yl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[378];7-(5-methylthiophen-2-yl)-2-(5-(5-(piperidin-1l-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[379];3,3-dimethyl-N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[380];N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[381];N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[382];N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[383];N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[384];N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[385];N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[386];N-benzyl-1-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[387];1-cyclopentyl-N-((5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[388];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridine[389];7-(5-methylthiophen-2-yl)-2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[390];N-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[391];N-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[392];1-(5-(2-(5-(5-aminopyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethanone[393];1-(5-(2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethanone[394];1-(5-(2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethanone[395];1-(5-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethanone[396];1-(5-(2-(5-(5-(dimethylamino)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethanone[397];N-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[398];N-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[399]; andN-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[400]; or a pharmaceutically acceptable salt thereof.
 18. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[401];1-(5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethanone[402];1-(5-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethanone[403];1-(5-(2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethanone[404];1-(5-(2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethanone[405];N-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[406];N-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[407];N-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[408];N-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[409];N-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[410];N-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[411];N-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[412];1-(5-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethanone[413];1-(5-(2-(5-(5-(((cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethanone[414];1-(5-(2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethanone[415];1-(5-(2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethanone[416];N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[417];N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[418];N-(3-(2-(5-(5-aminopyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide[419];N-(3-fluoro-5-(2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide[420];N-(3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide[421];N-(3-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide[422];N-(3-(2-(5-(5-(dimethylamino)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide[423];N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[424];N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[425];N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[426];N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[427];N-(3-fluoro-5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide [428];N-(3-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide [429];N-(3-fluoro-5-(2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide [430];N-(3-fluoro-5-(2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide [431];N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[432];N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[433];N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[434];N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[435];N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[436];N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[437];N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[438];N-(3-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide [439];N-(3-(2-(5-(5-(((cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide[440];N-(3-(2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide[441];N-(3-fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide [442];N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[443];N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[444];N¹-(3-(2-(5-(5-aminopyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[445];N¹-(3-fluoro-5-(2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[446];N¹-(3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[447];N¹-(3-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[448];N¹-(3-(2-(5-(5-(dimethylamino)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[449];N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[450];N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[451];N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[452];N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[453];N¹-(3-fluoro-5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[454];N¹-(3-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[455];N¹-(3-fluoro-5-(2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[456];N¹-(3-fluoro-5-(2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[457];N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[458];N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[459];N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[460];N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[461];N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[462];N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[463];N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[464];N¹-(3-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[465];N¹-(3-(2-(5-(5-(((cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[466];N¹-(3-(2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[467];N¹-(3-fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[468];1-(5-(7-fluoro-3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[481];1-(5-(7-fluoro-3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[741];N-(3-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-7-fluoro-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide[897];1-(5-(6-fluoro-3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[949];1-(5-(6-fluoro-3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[1209];N-(3-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-6-fluoro-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide[1365];1-(5-(4-fluoro-3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[1417];1-(5-(4-fluoro-3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[1677];N-(3-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-4-fluoro-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide[1833];7-(3-fluorophenyl)-2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1873];7-(3-fluorophenyl)-2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1874];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridine[1875];7-(3-fluorophenyl)-2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1876];2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-indazol-3-yl)-7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridine[1877];1-(6-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[1878];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridine[1879];7-(3-fluorophenyl)-2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1880];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1881];7-(3-fluorophenyl)-2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1882];2-((5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[1883];7-(3-fluorophenyl)-2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1884];5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[1885];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridine[1886];2-cyclohexyl-N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[1887];7-(3-fluorophenyl)-2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1888];7-(3-fluorophenyl)-2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1889];7-(3-fluorophenyl)-2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1890];7-(4-fluorophenyl)-2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1891];7-(4-fluorophenyl)-2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1892];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridine[1893];7-(4-fluorophenyl)-2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1894];2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-indazol-3-yl)-7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridine[1895];1-(6-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[1896];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridine[1897];7-(4-fluorophenyl)-2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1898];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1899]; and7-(4-fluorophenyl)-2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1900]; or a pharmaceutically acceptable salt thereof.
 19. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:2-((5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[1901];7-(4-fluorophenyl)-2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1902];5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[1903];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridine[1904];2-cyclohexyl-N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[1905];7-(4-fluorophenyl)-2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1906];7-(4-fluorophenyl)-2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1907];7-(4-fluorophenyl)-2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1908];7-(2-fluorophenyl)-2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1909];7-(2-fluorophenyl)-2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1910];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridine[1911];7-(2-fluorophenyl)-2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1912];2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-indazol-3-yl)-7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridine[1913];1-(6-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[1914];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridine[1915];7-(2-fluorophenyl)-2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1916];N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1917];7-(2-fluorophenyl)-2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1918];2-((5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[1919];7-(2-fluorophenyl)-2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1920];5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[1921];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridine[1922];2-cyclohexyl-N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[1923];7-(2-fluorophenyl)-2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1924];7-(2-fluorophenyl)-2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1925];7-(2-fluorophenyl)-2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1926];2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridine[1927];7-(pyridin-3-yl)-2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1928];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridine[1929];2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridine[1930];2-(5-(1,2-dimethyl-H-imidazol-5-yl)-1H-indazol-3-yl)-7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridine[1931];1-(6-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[1932];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridine[1933];2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridine[1934];2-(piperidin-4-yl)-N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[1935];7-(pyridin-3-yl)-2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1936];N,N-dimethyl-2-((5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)ethan-1-amine[1937];2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridine[1938];5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[1939];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridine[1940];2-cyclohexyl-N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[1941];7-(pyridin-3-yl)-2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1942];2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridine[1943];2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridine[1944];2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine[1945];7-(pyridin-4-yl)-2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1946];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine[1947];2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine[1948];2-(5-(1,2-dimethyl-H-imidazol-5-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine[1949];1-(6-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[1950];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine[1951];2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine[1952];2-(piperidin-4-yl)-N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[1953];7-(pyridin-4-yl)-2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1954];N,N-dimethyl-2-((5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)ethan-1-amine[1955];2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine[1956];5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[1957];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine[1958];2-cyclohexyl-N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[1959];7-(pyridin-4-yl)-2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1960];2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine[1961];2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine[1962];2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridine[1963];7-(pyridin-2-yl)-2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1964];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridine[1965];2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridine[1966];2-(5-(1,2-dimethyl-H-imidazol-5-yl)-1H-indazol-3-yl)-7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridine[1967];1-(6-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[1968];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridine[1969];2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridine[1970];2-(piperidin-4-yl)-N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[1971];7-(pyridin-2-yl)-2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1972];N,N-dimethyl-2-((5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)ethan-1-amine[1973];2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridine[1974];5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[1975];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridine[1976];2-cyclohexyl-N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[1977];7-(pyridin-2-yl)-2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1978];7-(pyridin-2-yl)-2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1979];2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridine[1980];7-(piperidin-1-yl)-2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1981];7-(piperidin-1-yl)-2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1982];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridine[1983];2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridine[1984];2-(5-(1,2-dimethyl-H-imidazol-5-yl)-1H-indazol-3-yl)-7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridine[1985];1-(6-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[1986];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridine[1987];7-(piperidin-1-yl)-2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1988];N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1989];7-(piperidin-1-yl)-2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1990];N,N-dimethyl-2-((5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)ethan-1-amine[1991];2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridine[1992];5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[1993];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridine[1994];2-cyclohexyl-N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[1995];7-(piperidin-1-yl)-2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1996];7-(piperidin-1-yl)-2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1997];7-(piperidin-1-yl)-2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1998];7-(4-methyl-1H-imidazol-1-yl)-2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[1999]; and7-(4-methyl-1H-imidazol-1-yl)-2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2000]; or a pharmaceutically acceptable salt thereof.
 20. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridine[2001];7-(4-methyl-1H-imidazol-1-yl)-2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2002];2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-indazol-3-yl)-7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridine[2003];1-(6-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[2004];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridine[2005];7-(4-methyl-1H-imidazol-1-yl)-2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2006];N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[2007];7-(4-methyl-1H-imidazol-1-yl)-2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2008];N,N-dimethyl-2-((5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)ethan-1-amine[2009];2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-7-(4-methyl-1H-idazol-3-yl)-7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridine[2010];5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[2011];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridine[2012];2-cyclohexyl-N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2013];7-(4-methyl-1H-imidazol-1-yl)-2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2014];7-(4-methyl-1H-imidazol-1-yl)-2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2015];7-(4-methyl-1H-imidazol-1-yl)-2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2016];7-(4-methylpiperazin-1-yl)-2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2017];7-(4-methylpiperazin-1-yl)-2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2018];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridine[2019];2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridine[2020];2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-indazol-3-yl)-7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridine[2021];1-(6-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[2022];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridine[2023];7-(4-methylpiperazin-1-yl)-2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2024];N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[2025];7-(4-methylpiperazin-1-yl)-2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2026];N,N-dimethyl-2-((5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)ethan-1-amine[2027];2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridine[2028];5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[2029];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridine[2030];2-cyclohexyl-N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2031];7-(4-methylpiperazin-1-yl)-2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2032];7-(4-methylpiperazin-1-yl)-2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2033];7-(4-methylpiperazin-1-yl)-2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2034]; 2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2035];2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2036];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2037];2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2038];2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2039];1-(6-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[2040];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2041];2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2042];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[2043];2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2044];2-((5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[2045];2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2046];5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[2047];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2048];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-cyclohexylacetamide[2049]; 2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2050]; 2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2051]; 2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2052];2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[2053];2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[2054];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[2055];2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[2056];2-(5-(1,2-dimethyl-H-imidazol-5-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[2057];1-(6-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[2058];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[2059];2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[2060];2-(piperidin-4-yl)-N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2061];2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[2062];N,N-dimethyl-2-((5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)ethan-1-amine[2063];2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[2064];5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[2065];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[2066];2-cyclohexyl-N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2067];2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[2068];2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[2069];2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[2070];7-(furan-3-yl)-2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2071];7-(furan-3-yl)-2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2072];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(furan-3-yl)-3H-imidazo[4,5-b]pyridine[2073];7-(furan-3-yl)-2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2074];2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-indazol-3-yl)-7-(furan-3-yl)-3H-imidazo[4,5-b]pyridine[2075];1-(6-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[2076];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(furan-3-yl)-3H-imidazo[4,5-b]pyridine[2077];7-(furan-3-yl)-2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2078];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[2079];7-(furan-3-yl)-2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2080];2-((5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[2081];7-(furan-3-yl)-2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2082];5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[2083];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(furan-3-yl)-3H-imidazo[4,5-b]pyridine[2084];2-cyclohexyl-N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2085];7-(furan-3-yl)-2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2086];7-(furan-3-yl)-2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2087];7-(furan-3-yl)-2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2088];2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2089];2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2090];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2091];2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2092];2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2093];1-(6-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[2094];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2095];2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2096];2-(piperidin-4-yl)-N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2097];2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2098];N,N-dimethyl-2-((5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)ethan-1-amine[2099]; and2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2100]; or a pharmaceutically acceptable salt thereof.
 21. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[2101];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2102];2-cyclohexyl-N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2103];2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2104];2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2105];2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2106];7-(5-fluorothiophen-2-yl)-2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2107];7-(5-fluorothiophen-2-yl)-2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2108];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2109];7-(5-fluorothiophen-2-yl)-2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2110];2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-indazol-3-yl)-7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2111];1-(6-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[2112];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2113];7-(5-fluorothiophen-2-yl)-2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2114];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[2115];7-(5-fluorothiophen-2-yl)-2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2116];2-((5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[2117];7-(5-fluorothiophen-2-yl)-2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2118];5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[2119];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2120];2-cyclohexyl-N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2121];7-(5-fluorothiophen-2-yl)-2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2122];7-(5-fluorothiophen-2-yl)-2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2123];7-(5-fluorothiophen-2-yl)-2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2124];7-(5-methylthiophen-2-yl)-2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2125];7-(5-methylthiophen-2-yl)-2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2126];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2127];2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2128];2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-H-indazol-3-yl)-7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2129];1-(6-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[2130];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2131];7-(5-methylthiophen-2-yl)-2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2132];N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[2133];7-(5-methylthiophen-2-yl)-2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2134];N,N-dimethyl-2-((5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)ethan-1-amine[2135];2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2136];5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[2137];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridine[2138];2-cyclohexyl-N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2139];7-(5-methylthiophen-2-yl)-2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2140];7-(5-methylthiophen-2-yl)-2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2141];7-(5-methylthiophen-2-yl)-2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2142];1-(5-(2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2143];1-(5-(2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2144];1-(5-(2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2145];1-(5-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2146];1-(5-(2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2147];1-(5-(2-(5-(6-(3-aminoazetidin-1-yl)pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2148];1-(5-(2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2149];1-(5-(2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2150];N-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[2151];1-(5-(2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2152];1-(5-(2-(5-(5-(2-(dimethylamino)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2153];1-(5-(2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2154];1-(5-(2-(5-(5-hydroxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2155];1-(5-(2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2156];N-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-cyclohexylacetamide[2157];1-(5-(2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2158];1-(5-(2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2159];1-(5-(2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)thiophen-2-yl)ethan-1-one[2160];N-(3-fluoro-5-(2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide[2161];N-(3-fluoro-5-(2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide[2162];N-(3-(2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide[2163];N-(3-fluoro-5-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide[2164];N-(3-(2-(5-(1,2-dimethyl-H-imidazol-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide[2165];N-(3-(2-(5-(6-(3-aminoazetidin-1-yl)pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide[2166];N-(3-(2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide[2167];N-(3-fluoro-5-(2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide[2168];N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[2169];N-(3-fluoro-5-(2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide[2170];N-(3-(2-(5-(5-(2-(dimethylamino)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide[2171];N-(3-fluoro-5-(2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide[2172];N-(3-fluoro-5-(2-(5-(5-hydroxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide[2173];N-(3-(2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide[2174];2-cyclohexyl-N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2175];N-(3-fluoro-5-(2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide[2176];N-(3-fluoro-5-(2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide[2177];N-(3-fluoro-5-(2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide[2178];N¹-(3-fluoro-5-(2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[2179];N¹-(3-fluoro-5-(2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N₂-dimethylethane-1,2-diamine[2180];N¹-(3-(2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[2181];N¹-(3-fluoro-5-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[2182];N¹-(3-(2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[2183];N¹-(3-(2-(5-(6-(3-aminoazetidin-1-yl)pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[2184];N¹-(3-(2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[2185];N¹-(3-fluoro-5-(2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[2186];N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[2187];N¹-(3-fluoro-5-(2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[2188];N¹-(3-(2-(5-(5-(2-(dimethylamino)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[2189];N₁-(3-fluoro-5-(2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[2190];5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[2191];N¹-(3-(2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[2192];2-cyclohexyl-N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2193];N¹-(3-fluoro-5-(2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[2194];N¹-(3-fluoro-5-(2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[2195];N¹-(3-fluoro-5-(2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[2196];N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[2197];N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[2198];5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[2199]; and2-(3-fluoro-5-(2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)-N,N-dimethylethan-1-amine[2200]; or a pharmaceutically acceptable salt thereof.
 22. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:2-(3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)-N,N-dimethylethan-1-amine[2201];2-(3-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[2202];5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N,N-dimethylpyridin-3-amine[2203];N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[2204];N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[2205];N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[2206];N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[2207];5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N-isopropylpyridin-3-amine[2208];2-(3-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[2209];2-(3-fluoro-5-(2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)-N,N-dimethylethan-1-amine[2210];2-(3-fluoro-5-(2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)-N,N-dimethylethan-1-amine[2211];N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[2212];N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[2213];N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[2214];N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[2215];N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[2216];N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[2217];N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[2218];2-(3-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[2219];2-(3-(2-(5-(5-(((cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[2220];2-(3-(2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[2221];2-(3-fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)-N,N-dimethylethan-1-amine[2222];2-(3-fluoro-5-(2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)-N,N-dimethylethan-1-amine[2223];2-(3-fluoro-5-(2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)-N,N-dimethylethan-1-amine[2224];2-(3-fluoro-5-(2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)-N,N-dimethylethan-1-amine[2225];2-(3-(2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[2226];2-(3-fluoro-5-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)-N,N-dimethylethan-1-amine[2227];2-(3-(2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[2228];1-(6-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[2229];2-(3-(2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[2230];2-(3-fluoro-5-(2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)-N,N-dimethylethan-1-amine[2231];N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[2232];2-(3-fluoro-5-(2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)-N,N-dimethylethan-1-amine[2233];2-((5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[2234];2-(3-fluoro-5-(2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)-N,N-dimethylethan-1-amine[2235];5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[2236];2-(3-(2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[2237];2-cyclohexyl-N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2238];2-(3-fluoro-5-(2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)-N,N-dimethylethan-1-amine[2239];2-(3-fluoro-5-(2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)-N,N-dimethylethan-1-amine[2240];N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[2241];N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[2242];5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[2243];7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2244];7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2245];N-((5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[2246];5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N,N-dimethylpyridin-3-amine[2247];N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[2248];N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[2249];N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[2250];N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[2251];5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N-isopropylpyridin-3-amine[2252];1-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[2253];7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2254];7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2-(5-(5-(piperidin-1l-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2255];N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[2256];N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[2257];N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[2258];N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[2259];N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[2260];N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[2261];N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[2262];N-benzyl-1-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[2263];1-cyclopentyl-N-((5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[2264];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridine[2265];7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2266];7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2267];7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2268];7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2269];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridine[2270];7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2271];2-(5-(1,2-dimethyl-H-imidazol-5-yl)-1H-indazol-3-yl)-7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridine[2272];1-(6-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[2273];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridine[2274];7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2275];N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[2276];7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2277];2-((5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[2278];7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2279];5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[2280];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridine[2281];2-cyclohexyl-N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2282];7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2283];7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine [2284];N-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[2285];N-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[2286];3-(2-(5-(5-aminopyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenol[2287];3-fluoro-5-(2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenol[2288];3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenol[2289];3-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenol[2290];3-(2-(5-(5-(dimethylamino)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenol[2291];N-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[2292];N-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[2293];N-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[2294];N-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[2295];3-fluoro-5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenol[2296];3-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenol[2297];3-fluoro-5-(2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenol[2298];3-fluoro-5-(2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenol[2299]; andN-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[2300]; or a pharmaceutically acceptable salt thereof.
 23. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[2301];N-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[2302];N-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[2303];N-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[2304];N-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[2305];N-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[2306];3-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenol[2307];3-(2-(5-(5-(((cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenol[2308];3-(2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenol[2309];3-fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenol[2310];3-fluoro-5-(2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenol[2311];3-fluoro-5-(2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenol[2312];3-fluoro-5-(2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenol[2313];3-(2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenol[2314];3-fluoro-5-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenol[2315];3-(2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenol[2316];3-(2-(5-(6-(3-aminoazetidin-1-yl)pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenol[2317];3-(2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenol[2318];3-fluoro-5-(2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenol[2319];N-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[2320];3-fluoro-5-(2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenol[2321];3-(2-(5-(5-(2-(dimethylamino)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenol[2322];3-fluoro-5-(2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenol[2323];5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[2324];3-(2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorophenol[2325];2-cyclohexyl-N-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2326];3-fluoro-5-(2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenol[2327];3-fluoro-5-(2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)phenol[2328];N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[2329];N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[2330];5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[2331];7-(3-fluoro-5-methoxyphenyl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2332];7-(3-fluoro-5-methoxyphenyl)-2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2333];N-((5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[2334];5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N,N-dimethylpyridin-3-amine[2335];N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[2336];N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[2337];N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-phenylacetamide[2338];N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[2339];5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N-isopropylpyridin-3-amine[2340];1-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[2341];7-(3-fluoro-5-methoxyphenyl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2342];7-(3-fluoro-5-methoxyphenyl)-2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2343];N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[2344];N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[2345];N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[2346];N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[2347];N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[2348];N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[2349];N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclohexanecarboxamide[2350];N-benzyl-1-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methanamine[2351];1-cyclopentyl-N-((5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)methanamine[2352];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridine[2353];7-(3-fluoro-5-methoxyphenyl)-2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2354];7-(3-fluoro-5-methoxyphenyl)-2-(5-(pyridin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2355];7-(3-fluoro-5-methoxyphenyl)-2-(5-(piperidin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2356];7-(3-fluoro-5-methoxyphenyl)-2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2357];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridine[2358];7-(3-fluoro-5-methoxyphenyl)-2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2359];2-(5-(1,2-dimethyl-H-imidazol-5-yl)-1H-indazol-3-yl)-7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridine[2360];1-(6-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyrazin-2-yl)azetidin-3-amine[2361];2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridine[2362];7-(3-fluoro-5-methoxyphenyl)-2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2363];N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[2364];7-(3-fluoro-5-methoxyphenyl)-2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2365];2-((5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[2366];7-(3-fluoro-5-methoxyphenyl)-2-(5-(5-methoxypyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2367];5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[2368];2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-indazol-3-yl)-7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridine [2369];2-cyclohexyl-N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2370];7-(3-fluoro-5-methoxyphenyl)-2-(5-(pyridin-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2371];7-(3-fluoro-5-methoxyphenyl)-2-(5-(pyrazin-2-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2372];2-(dimethylamino)-N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2373];2-(dimethylamino)-N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2374];2-(dimethylamino)-N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2375];2-(dimethylamino)-N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2376];2-(dimethylamino)-N-(5-(3-(7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2377];2-(dimethylamino)-N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2378];2-(dimethylamino)-N-(5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2379];2-(dimethylamino)-N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2380];2-(dimethylamino)-N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2381];N-(5-(3-(3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(dimethylamino)acetamide[2382];2-(dimethylamino)-N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2383];2-(dimethylamino)-N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2384];2-(dimethylamino)-N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2385];2-(dimethylamino)-N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2386];2-(dimethylamino)-N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2387];N-(5-(3-(7-(5-acetylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-2-(dimethylamino)acetamide[2388];2-(dimethylamino)-N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2389];2-(dimethylamino)-N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2390];2-(dimethylamino)-N-(5-(3-(7-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2391];2-(dimethylamino)-N-(5-(3-(7-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2392];2-(dimethylamino)-N-(5-(3-(7-(3-fluoro-5-hydroxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2393];2-(dimethylamino)-N-(5-(3-(7-(3-fluoro-5-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[2394];4-(2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)morpholine[2395];7-(4,4-difluoropiperidin-1-yl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine [2396];7-(1-methylpiperidin-4-yl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine [2397];4-(2-(5-(5-fluoropyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)morpholine [2398];2-(5-(5-fluoropyridin-3-yl)-1H-indazol-3-yl)-7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridine[2399];7-(4,4-difluoropiperidin-1-yl)-2-(5-(5-fluoropyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2400];2-(5-(5-fluoropyridin-3-yl)-1H-indazol-3-yl)-7-(1-methylpiperidin-4-yl)-3H-imidazo[4,5-b]pyridine[2401];2-(5-(5-fluoropyridin-3-yl)-1H-indazol-3-yl)-7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridine[2402];4-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)morpholine[2403];7-(4,4-difluoropiperidin-1-yl)-2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[2404];2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(1-methylpiperidin-4-yl)-3H-imidazo[4,5-b]pyridine[2405];4-(2-(5-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)morpholine[2406];2-(5-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridine[2407];2-(5-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(4,4-difluoropiperidin-1-yl)-3H-imidazo[4,5-b]pyridine[2408];2-(5-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(1-methylpiperidin-4-yl)-3H-imidazo[4,5-b]pyridine[2409];2-(5-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridine[2410];4-(2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)morpholine[2411];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(4,4-difluoropiperidin-1-yl)-3H-imidazo[4,5-b]pyridine[2412]; and2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(1-methylpiperidin-4-yl)-3H-imidazo[4,5-b]pyridine[2413]; or a pharmaceutically acceptable salt thereof.
 24. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[1];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[2];5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N,N-dimethylpyridin-3-amine[7];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[9];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[19];N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[21];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridine[25];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[28];7-(4-fluorophenyl)-2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[40];N-(5-(3-(7-(4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[46];5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[55];5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N,N-dimethylpyridin-3-amine[59];N-(5-(3-(7-(2-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[61];5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[81];7-(pyridin-3-yl)-2-(5-(pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[82];N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[87];2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-7-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine[109];N-(5-(3-(7-(pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[148];N,N-dimethyl-5-(3-(7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[163];2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-indazol-3-yl)-7-(piperidin-1-yl)-3H-imidazo[4,5-b]pyridine[181];3-methyl-N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide[184];N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[190];N-(5-(3-(7-(4-methyl-1H-imidazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[202];7-(4-methylpiperazin-1-yl)-2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridine[223];2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridine[265];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[268];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[269];2-phenyl-N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)acetamide[270];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)benzamide[271];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[277];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopropanecarboxamide[279];N-(5-(3-(7-(thiophen-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[281];N-((5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)methyl)ethanamine[292];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[295];5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)-N-isopropylpyridin-3-amine[298];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[304];N-(5-(3-(7-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[306];N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)propionamide[313];N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[320];N-(5-(3-(7-(thiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclopentanecarboxamide[333];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide[340];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[346];N-(5-(3-(7-(5-fluorothiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)cyclobutanecarboxamide[358];5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-amine[367];N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pivalamide[372];N-(5-(3-(7-(5-methylthiophen-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)isobutyramide[373];N-(3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide[421];N-(5-(3-(7-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butyramide[433];N-(3-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-5-fluorobenzyl)methanesulfonamide[439];N-(3-fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-indazol-3-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)methanesulfonamide[442];N-(5-(3-(7-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)pentanamide[460];2-(5-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridine[1875]; and5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-ol[1885]; or a pharmaceutically acceptable salt thereof.
 25. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:

a pharmaceutically acceptable salt thereof.
 26. The method of claim 1,wherein the bone or cartilage disease is osteoarthritis.
 27. The methodof claim 1, wherein the bone or cartilage disease is articular cartilage(chondral) defects.
 28. The method of claim 1, wherein the bone orcartilage disease is degenerative disc disease.
 29. The method of claim1, wherein the bone or cartilage disease is relapsing polychondritis.30. The method of claim 1, wherein the bone or cartilage disease isosteochondritis dissecans.
 31. The method of claim 1, wherein thesubject is a human.